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Papers by Safa BOUJEMAA

Research paper thumbnail of S941 Comparative Efficacy and Safety of Adalimumab vs Vedolizumab in Managing Moderate-to-Severe Crohn's Disease: A Systematic Review and Meta-Analysis

S941 Comparative Efficacy and Safety of Adalimumab vs Vedolizumab in Managing Moderate-to-Severe Crohn's Disease: A Systematic Review and Meta-Analysis

The American Journal of Gastroenterology, Sep 30, 2023

Research paper thumbnail of Comparing the Efficacy and Safety of Adalimumab and Vedolizumab in Treating Moderate to Severe Crohn’s Disease and Ulcerative Colitis

Gastroenterology Research, Nov 30, 2023

Background: Numerous patients with inflammatory bowel disease (IBD) do not respond to conventiona... more Background: Numerous patients with inflammatory bowel disease (IBD) do not respond to conventional or biological therapy. Adalimumab (ADA) and vedolizumab (VDZ), according to certain research, may be a useful alternative treatment for these people. The purpose of this study was to assess the effectiveness and safety of using ADA and VDZ to treat moderate to severe IBD: Crohn's disease (CD) and ulcerative colitis (UC). We searched PubMed, Medline, Web of Science, Scopus, the Cochrane Library, Embase, Google Scholar, CINAHL, Clinicaltrials.gov, and WHO trials registry (ICTRP). Randomized controlled trials (RCTs) comparing ADA or VDZ with placebo in participants with active CD or UC were included. The primary outcomes were the clinical response and remission at induction and maintenance phases and mucosal healing. The secondary outcome was the incidence of profound negative events. The research used Comprehensive Meta-Analysis version 3 (Biostat Inc., USA). Results: Eighteen RCTs were incorporated, in which 11 studies described the usefulness and safeness of ADA or VDZ in CD patients, and seven studies investigated the efficacy and safety of ADA or VDZ in UC patients. The meta-analysis revealed that both ADA and VDZ treatments were superior to placebo for producing clinical remission and eliciting clinical response at induction and maintenance phases in individuals with moderately to severely active CD or UC. Interestingly, we found that ADA was superior to VDZ as first-line treatment for patients with CD, but not UC. ADA and VDZ are effective and safe in CD and UC patients. However, RCTs of a larger number of patients are still required for better assessing the safety profile of ADA and VDZ.

Research paper thumbnail of S942 Systematic Review and Meta-Analysis Comparing Adalimumab and Vedolizumab in Treating Moderate to Severe Ulcerative Colitis: Effectiveness and Safety

S942 Systematic Review and Meta-Analysis Comparing Adalimumab and Vedolizumab in Treating Moderate to Severe Ulcerative Colitis: Effectiveness and Safety

The American Journal of Gastroenterology, Sep 30, 2023

Research paper thumbnail of Diagnostic evaluation of Panbio™ antigen rapid diagnostic test for SARS‐CoV‐2: A systematic review and meta-analysis

Diagnostic evaluation of Panbio™ antigen rapid diagnostic test for SARS‐CoV‐2: A systematic review and meta-analysis

Journal of Virological Methods

Research paper thumbnail of Protein Induced by Vitamin K Absence or Antagonist-II Versus Alpha-Fetoprotein in the Diagnosis of Hepatocellular Carcinoma: A Systematic Review With Meta-Analysis

Journal of Clinical Medicine Research, Jul 1, 2023

Background: Protein induced by vitamin K absence or antagonist-II (PIVKA-II) and α-fetoprotein (A... more Background: Protein induced by vitamin K absence or antagonist-II (PIVKA-II) and α-fetoprotein (AFP) are promising tumor markers for the diagnosis of hepatocellular carcinoma (HCC). Yet, their diagnostic performance differs throughout HCC investigations. The aim of this meta-analysis was to assess the effectiveness of PIVKA-II and AFP in the diagnosis of HCC. Methods: A systematic literature search was performed to identify relevant studies from eight databases, which were published up to February 2023, in order to compare the diagnostic performance of PIVKA-II and AFP for HCC. Pooled sensitivity and specificity were calculated. Summary receiver operating characteristic (SROC) curve was performed to assess the diagnostic accuracy of each biomarker. Results: Fifty-three studies were identified. The pooled sensitivity (95% confidence interval (CI)) of PIVKA-II and AFP was 0.71 (0.70-0.72) and 0.64 (0.63-0.65), respectively in diagnosis of HCC, and the corresponding pooled specificity (95% CI) was 0.90 (0.89-0.90) and 0.87 (0.87-0.88), respectively. The area under the ROC curve (AUC) of PIVKA-II and AFP was 0.89 (0.88-0.90) and 0.78 (0.77-0.79), respectively. Subgroup analysis demonstrated that PIVKA-II presented higher AUC values compared to AFP in terms of ethnic group (African, European, Asian, and American patients), etiology (mixed-type HCC, hepatitis C virus (HCV)-related, and hepatitis B virus (HBV)-related) and sample size of cases (≤ 100 and > 100). Conclusion: This study reveals that PIVKA-II is a promising biomarker for identifying and tracking HCC, exhibiting greater accuracy than AFP. Our findings indicate that PIVKA-II outperforms AFP in detecting HCC across diverse racial groups and sample sizes, as well as in cases of HBV-related, HCV-related, or mixed-etiology HCC.

Research paper thumbnail of Protein induced by vitamin K absence or antagonist-II production is a strong predictive marker for extrahepatic metastases in early hepatocellular carcinoma: a prospective evaluation

BMC Cancer, 2011

Background Clinicians often experience extrahepatic metastases associated with hepatocellular car... more Background Clinicians often experience extrahepatic metastases associated with hepatocellular carcinoma (HCC), even if no evidence of intrahepatic recurrence after treatment is observed. We investigated the pretreatment predictors of extrahepatic metastases in HCC patients. Methods Patients diagnosed with HCC without evidence of extrahepatic metastases were prospectively enrolled. We evaluated the correlation between extrahepatic metastases and pretreatment clinical variables, including serum tumor markers. Results A total of 354 patients were included. Seventy-six patients (21%) had extrahepatic metastases during the observation period (median, 25.3 months; range, 0.6-51.3 months). Cox regression multivariate analysis showed that serum protein induced by vitamin K absence or antagonist-II (PIVKA-II) production levels, the intrahepatic tumor stage, platelet count, and portal vein thrombosis were independent risk factors for extrahepatic metastases. Patients with a PIVKA-II productio...

Research paper thumbnail of Association between genital mycoplasmas (Ureaplasma urealyticum and Mycoplasma hominis) and HIV infection: a systematic review and meta-analysis

Association between genital mycoplasmas (Ureaplasma urealyticum and Mycoplasma hominis) and HIV infection: a systematic review and meta-analysis

Aids Reviews

Research paper thumbnail of MOESM2 of Spread of multidrug resistance among Ureaplasma serovars, Tunisia

MOESM2 of Spread of multidrug resistance among Ureaplasma serovars, Tunisia

Additional file 2: File S1. Multiple sequence alignment of the 5′-end of mba gene of the referenc... more Additional file 2: File S1. Multiple sequence alignment of the 5′-end of mba gene of the reference strain UPA1 and 19 Ureaplasma serovar 1 clinical strains. File S2. Multiple sequence alignment of the 5′-end of mba gene of the reference strain UPA3 and 35 Ureaplasma serovar 3 clinical strains. File S3. Multiple sequence alignment of the 5′-end of mba gene of the reference strain UPA6 and 19 Ureaplasma serovar 6 clinical strains. File S4. Multiple sequence alignment of the 5′-end of mba gene of the reference strains UUR4, UUR10, UUR12, UUR13 and 19 Ureaplasma serovars 4, 10, 12, 13 clinical strains. File S5. Multiple sequence alignment of the 5′-end of mba gene of the reference strains UUR2, UUR5, UUR8, UUR9 and 19 Ureaplasma serovars 2, 5, 8, 9 clinical strains. File S6. Partial sequence alignment of ParC protein of 26 Ureaplasma isolates resistant to fluoroquinolones (ParC_consensus correspond to ParC protein of UPA3 and UUR8 reference strains). File S7. Partial sequence alignment ...

Research paper thumbnail of MOESM1 of Spread of multidrug resistance among Ureaplasma serovars, Tunisia

MOESM1 of Spread of multidrug resistance among Ureaplasma serovars, Tunisia

Additional file 1: Table S1. Genes and respective flanking oligonucleotide primers used. Table S2... more Additional file 1: Table S1. Genes and respective flanking oligonucleotide primers used. Table S2. Epidemiologic characteristics of Ureaplasma spp. strains used. Table S3. In-vitro activity of tetracyclines, fluoroquinolones, and macrolides against 101 human Ureaplasma spp. isolates. Table S4. Distribution of antimicrobial resistance among patients with genital tract infections and infertility. Figure S5. PCR results screening for tet (M) (A) and Int-Tn genes (B) on 2% agarose gel. A. MW: GeneRuler 100 base pairs (bp) DNA Ladder. Lane 1: Negative control. Lane 2–13: Amplicons from the tetracycline-resistant Ureaplasma spp. clinical isolates. Lane 14–15: Amplicons from U. parvum ATCC 27815 and U. urealyticum ATCC 27618. Lane 16–21: Amplicons from tetracycline-sensitive Ureaplasma spp. clinical isolates. The tet (M) expected gene product is 397 bp based on the primers used. B. MW: GeneRuler 100 (bp) DNA Ladder. Lane 1: Negative control. Lane 2: Amplicon from a tetracycline-sensitive U...

Research paper thumbnail of P42- Association between genetic variation of Tunisian mycoplasma hominis isolates and tetracycline resistance

P42- Association between genetic variation of Tunisian mycoplasma hominis isolates and tetracycline resistance

Research paper thumbnail of Clonal Dissemination of Antibiotic Resistance Among Tunisian Mycoplasma Gallisepticum Isolates as Revealed By Gene-Targeted Sequencing Analysis

Clonal Dissemination of Antibiotic Resistance Among Tunisian Mycoplasma Gallisepticum Isolates as Revealed By Gene-Targeted Sequencing Analysis

Avian Diseases

Research paper thumbnail of Clonal Spread of Tetracycline Resistance Among Mycoplasma hominis Clinical Strains, Tunisia

Infection and Drug Resistance

Antimicrobial resistance in a number of bacterial pathogens has been shown to spread clonally. To... more Antimicrobial resistance in a number of bacterial pathogens has been shown to spread clonally. To our knowledge, data about the phylodistribution of drug resistance in Mycoplasma hominis are very scarce. The aims of this study were to assess the antimicrobial susceptibility of Mycoplasma hominis clinical strains in Tunisia, to identify the molecular basis of antibiotic resistance, and to investigate the phylogenetic relationships of resistant strains. This study included 65 molecularly typed Mycoplasma hominis clinical strains recovered from Tunisian patients over 18 years (2000-2018). The antimicrobial susceptibility was tested against nine antibacterial agents using the broth microdilution method. Minimum spanning tree was constructed to establish the phylogenetic relationships among resistant isolates. Fluoroquinolones, doxycycline, and josamycine were found to be the most effective antibacterial agents. However, 22 strains belonging to 11 expanded multilocus sequence types (eSTs) proved resistant to tetracycline. The majority of these eSTs were genetically related, indicative of clonal expansion of tetracycline resistance. The present study provides relevant information on the antibiotic susceptibility of Tunisian M. hominis clinical strains, lending support to a clonal transmission of tetracycline resistance. This is likely to have an important implication in monitoring the spread of drug resistance among M. hominis.

Research paper thumbnail of Spread of multidrug resistance among Ureaplasma serovars, Tunisia

Antimicrobial Resistance & Infection Control

Background Ureaplasma spp. have been implicated in a variety of clinical conditions and certain s... more Background Ureaplasma spp. have been implicated in a variety of clinical conditions and certain serovars are likely to be disease-associated. Hence, the ascending trend of Ureaplasma spp. resistance to antimicrobials should deserve more attention. Here we assessed the extent of antimicrobial resistance of Ureaplasma serovars in Tunisia, and investigated the underlying molecular basis. Methods This study included 101 molecularly typed Ureaplasma spp. clinical strains isolated over a 12-year time period (2005–2017). The antimicrobial susceptibility was tested against nine antibacterial agents using the broth microdilution method. Neighbor-joining tree was constructed to establish the phylogenetic relationships among isolates. Results We found that all ureaplasma isolates were resistant to ciprofloxacin and erythromycin, intermediately resistant to azithromycin, and susceptible to doxycycline, moxifloxacin and josamycin. Ofloxacin and levofloxacin resistance was found in 73.27 and 17.8...

Research paper thumbnail of Phylogenetics of Mycoplasma hominis clinical strains associated with gynecological infections or infertility as disclosed by an expanded multilocus sequence typing scheme

Scientific Reports

To our knowledge, the phylodistribution of M. hominis clinical strains associated with various pa... more To our knowledge, the phylodistribution of M. hominis clinical strains associated with various pathological conditions of the urogenital tract has not been explored hitherto. Here we analyzed the genetic diversity and phylogenetic relationships among 59 M. hominis Tunisian clinical isolates, categorized as gynecological infections-or infertility-associated pathotypes. For this purpose, we developed an expanded multilocus sequence typing (eMLST) scheme, combining the previously reported multilocus sequence typing (MLST) loci (gyrB, tuf, ftsY, uvrA, gap) with a new selected set of putative virulence genes (p120', vaa, lmp1, lmp3, p60), referred herein to as multi-virulence-locus sequence typing (MVLST) loci. In doing so, M. hominis population was segregated into two distinct genetic lineages, which were differentially associated with each pathotype. Such a clear dichotomy was supported by several phylogenetic and population genetic analysis tools. Recombination was found to take place, but not sufficient enough to break down the overall clonal population structure of M. hominis, most likely as a result of purifying selection, which accommodated the most fit clones. In sum, and owing to the eMLST scheme described herein, we provide insightful data on the phylogenetics of M. hominis, arguing for the existence of genetically differentiable urogenital pathotypes. Mycoplasma hominis, which belongs to the Mycoplasmataceae family, in the Mollicutes class, was the first mycoplasma species isolated from humans in 1937 1. It resides, as a commensal, in the lower urogenital tract of healthy persons. Under certain circumstances, M. hominis can cause a variety of genital infections such as bacterial vaginosis, pelvic inflammatory disease, and cervicitis 2. This microorganism seems to be associated with pregnancy complications and neonatal diseases 3. In addition, several studies reported the pathogenic role of M. hominis in infertility 4,5. More interestingly, this species has been linked to a wide range of extragenital infections (septic arthritis, endocarditis, brain abscess), especially in immunocompromised patients 6-8. To better understand the epidemiology and the mode of spread of M. hominis, several molecular typing systems have been developed. These include Pulse-Field Gel Electrophoresis (PFGE), Restriction Fragment Length Polymorphism (RFLP) analysis, Amplified Fragment Length Polymorphism (AFLP), and Random Amplified Polymorphic DNA (RADP). All these methods have revealed a high degree of both genetic and antigenic heterogeneity among M. hominis strains 9-12. Although informative, these approaches proved to be quite difficult to

Research paper thumbnail of Phylogenetics of Mycoplasma hominis clinical strains associated with gynecological infections or infertility as disclosed by an expanded multilocus sequence typing scheme

Scientific Reports

To our knowledge, the phylodistribution of M. hominis clinical strains associated with various pa... more To our knowledge, the phylodistribution of M. hominis clinical strains associated with various pathological conditions of the urogenital tract has not been explored hitherto. Here we analyzed the genetic diversity and phylogenetic relationships among 59 M. hominis Tunisian clinical isolates, categorized as gynecological infections-or infertility-associated pathotypes. For this purpose, we developed an expanded multilocus sequence typing (eMLST) scheme, combining the previously reported multilocus sequence typing (MLST) loci (gyrB, tuf, ftsY, uvrA, gap) with a new selected set of putative virulence genes (p120', vaa, lmp1, lmp3, p60), referred herein to as multi-virulence-locus sequence typing (MVLST) loci. In doing so, M. hominis population was segregated into two distinct genetic lineages, which were differentially associated with each pathotype. Such a clear dichotomy was supported by several phylogenetic and population genetic analysis tools. Recombination was found to take place, but not sufficient enough to break down the overall clonal population structure of M. hominis, most likely as a result of purifying selection, which accommodated the most fit clones. In sum, and owing to the eMLST scheme described herein, we provide insightful data on the phylogenetics of M. hominis, arguing for the existence of genetically differentiable urogenital pathotypes. Mycoplasma hominis, which belongs to the Mycoplasmataceae family, in the Mollicutes class, was the first mycoplasma species isolated from humans in 1937 1. It resides, as a commensal, in the lower urogenital tract of healthy persons. Under certain circumstances, M. hominis can cause a variety of genital infections such as bacterial vaginosis, pelvic inflammatory disease, and cervicitis 2. This microorganism seems to be associated with pregnancy complications and neonatal diseases 3. In addition, several studies reported the pathogenic role of M. hominis in infertility 4,5. More interestingly, this species has been linked to a wide range of extragenital infections (septic arthritis, endocarditis, brain abscess), especially in immunocompromised patients 6-8. To better understand the epidemiology and the mode of spread of M. hominis, several molecular typing systems have been developed. These include Pulse-Field Gel Electrophoresis (PFGE), Restriction Fragment Length Polymorphism (RFLP) analysis, Amplified Fragment Length Polymorphism (AFLP), and Random Amplified Polymorphic DNA (RADP). All these methods have revealed a high degree of both genetic and antigenic heterogeneity among M. hominis strains 9-12. Although informative, these approaches proved to be quite difficult to

Research paper thumbnail of S941 Comparative Efficacy and Safety of Adalimumab vs Vedolizumab in Managing Moderate-to-Severe Crohn's Disease: A Systematic Review and Meta-Analysis

S941 Comparative Efficacy and Safety of Adalimumab vs Vedolizumab in Managing Moderate-to-Severe Crohn's Disease: A Systematic Review and Meta-Analysis

The American Journal of Gastroenterology, Sep 30, 2023

Research paper thumbnail of Comparing the Efficacy and Safety of Adalimumab and Vedolizumab in Treating Moderate to Severe Crohn’s Disease and Ulcerative Colitis

Gastroenterology Research, Nov 30, 2023

Background: Numerous patients with inflammatory bowel disease (IBD) do not respond to conventiona... more Background: Numerous patients with inflammatory bowel disease (IBD) do not respond to conventional or biological therapy. Adalimumab (ADA) and vedolizumab (VDZ), according to certain research, may be a useful alternative treatment for these people. The purpose of this study was to assess the effectiveness and safety of using ADA and VDZ to treat moderate to severe IBD: Crohn's disease (CD) and ulcerative colitis (UC). We searched PubMed, Medline, Web of Science, Scopus, the Cochrane Library, Embase, Google Scholar, CINAHL, Clinicaltrials.gov, and WHO trials registry (ICTRP). Randomized controlled trials (RCTs) comparing ADA or VDZ with placebo in participants with active CD or UC were included. The primary outcomes were the clinical response and remission at induction and maintenance phases and mucosal healing. The secondary outcome was the incidence of profound negative events. The research used Comprehensive Meta-Analysis version 3 (Biostat Inc., USA). Results: Eighteen RCTs were incorporated, in which 11 studies described the usefulness and safeness of ADA or VDZ in CD patients, and seven studies investigated the efficacy and safety of ADA or VDZ in UC patients. The meta-analysis revealed that both ADA and VDZ treatments were superior to placebo for producing clinical remission and eliciting clinical response at induction and maintenance phases in individuals with moderately to severely active CD or UC. Interestingly, we found that ADA was superior to VDZ as first-line treatment for patients with CD, but not UC. ADA and VDZ are effective and safe in CD and UC patients. However, RCTs of a larger number of patients are still required for better assessing the safety profile of ADA and VDZ.

Research paper thumbnail of S942 Systematic Review and Meta-Analysis Comparing Adalimumab and Vedolizumab in Treating Moderate to Severe Ulcerative Colitis: Effectiveness and Safety

S942 Systematic Review and Meta-Analysis Comparing Adalimumab and Vedolizumab in Treating Moderate to Severe Ulcerative Colitis: Effectiveness and Safety

The American Journal of Gastroenterology, Sep 30, 2023

Research paper thumbnail of Diagnostic evaluation of Panbio™ antigen rapid diagnostic test for SARS‐CoV‐2: A systematic review and meta-analysis

Diagnostic evaluation of Panbio™ antigen rapid diagnostic test for SARS‐CoV‐2: A systematic review and meta-analysis

Journal of Virological Methods

Research paper thumbnail of Protein Induced by Vitamin K Absence or Antagonist-II Versus Alpha-Fetoprotein in the Diagnosis of Hepatocellular Carcinoma: A Systematic Review With Meta-Analysis

Journal of Clinical Medicine Research, Jul 1, 2023

Background: Protein induced by vitamin K absence or antagonist-II (PIVKA-II) and α-fetoprotein (A... more Background: Protein induced by vitamin K absence or antagonist-II (PIVKA-II) and α-fetoprotein (AFP) are promising tumor markers for the diagnosis of hepatocellular carcinoma (HCC). Yet, their diagnostic performance differs throughout HCC investigations. The aim of this meta-analysis was to assess the effectiveness of PIVKA-II and AFP in the diagnosis of HCC. Methods: A systematic literature search was performed to identify relevant studies from eight databases, which were published up to February 2023, in order to compare the diagnostic performance of PIVKA-II and AFP for HCC. Pooled sensitivity and specificity were calculated. Summary receiver operating characteristic (SROC) curve was performed to assess the diagnostic accuracy of each biomarker. Results: Fifty-three studies were identified. The pooled sensitivity (95% confidence interval (CI)) of PIVKA-II and AFP was 0.71 (0.70-0.72) and 0.64 (0.63-0.65), respectively in diagnosis of HCC, and the corresponding pooled specificity (95% CI) was 0.90 (0.89-0.90) and 0.87 (0.87-0.88), respectively. The area under the ROC curve (AUC) of PIVKA-II and AFP was 0.89 (0.88-0.90) and 0.78 (0.77-0.79), respectively. Subgroup analysis demonstrated that PIVKA-II presented higher AUC values compared to AFP in terms of ethnic group (African, European, Asian, and American patients), etiology (mixed-type HCC, hepatitis C virus (HCV)-related, and hepatitis B virus (HBV)-related) and sample size of cases (≤ 100 and > 100). Conclusion: This study reveals that PIVKA-II is a promising biomarker for identifying and tracking HCC, exhibiting greater accuracy than AFP. Our findings indicate that PIVKA-II outperforms AFP in detecting HCC across diverse racial groups and sample sizes, as well as in cases of HBV-related, HCV-related, or mixed-etiology HCC.

Research paper thumbnail of Protein induced by vitamin K absence or antagonist-II production is a strong predictive marker for extrahepatic metastases in early hepatocellular carcinoma: a prospective evaluation

BMC Cancer, 2011

Background Clinicians often experience extrahepatic metastases associated with hepatocellular car... more Background Clinicians often experience extrahepatic metastases associated with hepatocellular carcinoma (HCC), even if no evidence of intrahepatic recurrence after treatment is observed. We investigated the pretreatment predictors of extrahepatic metastases in HCC patients. Methods Patients diagnosed with HCC without evidence of extrahepatic metastases were prospectively enrolled. We evaluated the correlation between extrahepatic metastases and pretreatment clinical variables, including serum tumor markers. Results A total of 354 patients were included. Seventy-six patients (21%) had extrahepatic metastases during the observation period (median, 25.3 months; range, 0.6-51.3 months). Cox regression multivariate analysis showed that serum protein induced by vitamin K absence or antagonist-II (PIVKA-II) production levels, the intrahepatic tumor stage, platelet count, and portal vein thrombosis were independent risk factors for extrahepatic metastases. Patients with a PIVKA-II productio...

Research paper thumbnail of Association between genital mycoplasmas (Ureaplasma urealyticum and Mycoplasma hominis) and HIV infection: a systematic review and meta-analysis

Association between genital mycoplasmas (Ureaplasma urealyticum and Mycoplasma hominis) and HIV infection: a systematic review and meta-analysis

Aids Reviews

Research paper thumbnail of MOESM2 of Spread of multidrug resistance among Ureaplasma serovars, Tunisia

MOESM2 of Spread of multidrug resistance among Ureaplasma serovars, Tunisia

Additional file 2: File S1. Multiple sequence alignment of the 5′-end of mba gene of the referenc... more Additional file 2: File S1. Multiple sequence alignment of the 5′-end of mba gene of the reference strain UPA1 and 19 Ureaplasma serovar 1 clinical strains. File S2. Multiple sequence alignment of the 5′-end of mba gene of the reference strain UPA3 and 35 Ureaplasma serovar 3 clinical strains. File S3. Multiple sequence alignment of the 5′-end of mba gene of the reference strain UPA6 and 19 Ureaplasma serovar 6 clinical strains. File S4. Multiple sequence alignment of the 5′-end of mba gene of the reference strains UUR4, UUR10, UUR12, UUR13 and 19 Ureaplasma serovars 4, 10, 12, 13 clinical strains. File S5. Multiple sequence alignment of the 5′-end of mba gene of the reference strains UUR2, UUR5, UUR8, UUR9 and 19 Ureaplasma serovars 2, 5, 8, 9 clinical strains. File S6. Partial sequence alignment of ParC protein of 26 Ureaplasma isolates resistant to fluoroquinolones (ParC_consensus correspond to ParC protein of UPA3 and UUR8 reference strains). File S7. Partial sequence alignment ...

Research paper thumbnail of MOESM1 of Spread of multidrug resistance among Ureaplasma serovars, Tunisia

MOESM1 of Spread of multidrug resistance among Ureaplasma serovars, Tunisia

Additional file 1: Table S1. Genes and respective flanking oligonucleotide primers used. Table S2... more Additional file 1: Table S1. Genes and respective flanking oligonucleotide primers used. Table S2. Epidemiologic characteristics of Ureaplasma spp. strains used. Table S3. In-vitro activity of tetracyclines, fluoroquinolones, and macrolides against 101 human Ureaplasma spp. isolates. Table S4. Distribution of antimicrobial resistance among patients with genital tract infections and infertility. Figure S5. PCR results screening for tet (M) (A) and Int-Tn genes (B) on 2% agarose gel. A. MW: GeneRuler 100 base pairs (bp) DNA Ladder. Lane 1: Negative control. Lane 2–13: Amplicons from the tetracycline-resistant Ureaplasma spp. clinical isolates. Lane 14–15: Amplicons from U. parvum ATCC 27815 and U. urealyticum ATCC 27618. Lane 16–21: Amplicons from tetracycline-sensitive Ureaplasma spp. clinical isolates. The tet (M) expected gene product is 397 bp based on the primers used. B. MW: GeneRuler 100 (bp) DNA Ladder. Lane 1: Negative control. Lane 2: Amplicon from a tetracycline-sensitive U...

Research paper thumbnail of P42- Association between genetic variation of Tunisian mycoplasma hominis isolates and tetracycline resistance

P42- Association between genetic variation of Tunisian mycoplasma hominis isolates and tetracycline resistance

Research paper thumbnail of Clonal Dissemination of Antibiotic Resistance Among Tunisian Mycoplasma Gallisepticum Isolates as Revealed By Gene-Targeted Sequencing Analysis

Clonal Dissemination of Antibiotic Resistance Among Tunisian Mycoplasma Gallisepticum Isolates as Revealed By Gene-Targeted Sequencing Analysis

Avian Diseases

Research paper thumbnail of Clonal Spread of Tetracycline Resistance Among Mycoplasma hominis Clinical Strains, Tunisia

Infection and Drug Resistance

Antimicrobial resistance in a number of bacterial pathogens has been shown to spread clonally. To... more Antimicrobial resistance in a number of bacterial pathogens has been shown to spread clonally. To our knowledge, data about the phylodistribution of drug resistance in Mycoplasma hominis are very scarce. The aims of this study were to assess the antimicrobial susceptibility of Mycoplasma hominis clinical strains in Tunisia, to identify the molecular basis of antibiotic resistance, and to investigate the phylogenetic relationships of resistant strains. This study included 65 molecularly typed Mycoplasma hominis clinical strains recovered from Tunisian patients over 18 years (2000-2018). The antimicrobial susceptibility was tested against nine antibacterial agents using the broth microdilution method. Minimum spanning tree was constructed to establish the phylogenetic relationships among resistant isolates. Fluoroquinolones, doxycycline, and josamycine were found to be the most effective antibacterial agents. However, 22 strains belonging to 11 expanded multilocus sequence types (eSTs) proved resistant to tetracycline. The majority of these eSTs were genetically related, indicative of clonal expansion of tetracycline resistance. The present study provides relevant information on the antibiotic susceptibility of Tunisian M. hominis clinical strains, lending support to a clonal transmission of tetracycline resistance. This is likely to have an important implication in monitoring the spread of drug resistance among M. hominis.

Research paper thumbnail of Spread of multidrug resistance among Ureaplasma serovars, Tunisia

Antimicrobial Resistance & Infection Control

Background Ureaplasma spp. have been implicated in a variety of clinical conditions and certain s... more Background Ureaplasma spp. have been implicated in a variety of clinical conditions and certain serovars are likely to be disease-associated. Hence, the ascending trend of Ureaplasma spp. resistance to antimicrobials should deserve more attention. Here we assessed the extent of antimicrobial resistance of Ureaplasma serovars in Tunisia, and investigated the underlying molecular basis. Methods This study included 101 molecularly typed Ureaplasma spp. clinical strains isolated over a 12-year time period (2005–2017). The antimicrobial susceptibility was tested against nine antibacterial agents using the broth microdilution method. Neighbor-joining tree was constructed to establish the phylogenetic relationships among isolates. Results We found that all ureaplasma isolates were resistant to ciprofloxacin and erythromycin, intermediately resistant to azithromycin, and susceptible to doxycycline, moxifloxacin and josamycin. Ofloxacin and levofloxacin resistance was found in 73.27 and 17.8...

Research paper thumbnail of Phylogenetics of Mycoplasma hominis clinical strains associated with gynecological infections or infertility as disclosed by an expanded multilocus sequence typing scheme

Scientific Reports

To our knowledge, the phylodistribution of M. hominis clinical strains associated with various pa... more To our knowledge, the phylodistribution of M. hominis clinical strains associated with various pathological conditions of the urogenital tract has not been explored hitherto. Here we analyzed the genetic diversity and phylogenetic relationships among 59 M. hominis Tunisian clinical isolates, categorized as gynecological infections-or infertility-associated pathotypes. For this purpose, we developed an expanded multilocus sequence typing (eMLST) scheme, combining the previously reported multilocus sequence typing (MLST) loci (gyrB, tuf, ftsY, uvrA, gap) with a new selected set of putative virulence genes (p120', vaa, lmp1, lmp3, p60), referred herein to as multi-virulence-locus sequence typing (MVLST) loci. In doing so, M. hominis population was segregated into two distinct genetic lineages, which were differentially associated with each pathotype. Such a clear dichotomy was supported by several phylogenetic and population genetic analysis tools. Recombination was found to take place, but not sufficient enough to break down the overall clonal population structure of M. hominis, most likely as a result of purifying selection, which accommodated the most fit clones. In sum, and owing to the eMLST scheme described herein, we provide insightful data on the phylogenetics of M. hominis, arguing for the existence of genetically differentiable urogenital pathotypes. Mycoplasma hominis, which belongs to the Mycoplasmataceae family, in the Mollicutes class, was the first mycoplasma species isolated from humans in 1937 1. It resides, as a commensal, in the lower urogenital tract of healthy persons. Under certain circumstances, M. hominis can cause a variety of genital infections such as bacterial vaginosis, pelvic inflammatory disease, and cervicitis 2. This microorganism seems to be associated with pregnancy complications and neonatal diseases 3. In addition, several studies reported the pathogenic role of M. hominis in infertility 4,5. More interestingly, this species has been linked to a wide range of extragenital infections (septic arthritis, endocarditis, brain abscess), especially in immunocompromised patients 6-8. To better understand the epidemiology and the mode of spread of M. hominis, several molecular typing systems have been developed. These include Pulse-Field Gel Electrophoresis (PFGE), Restriction Fragment Length Polymorphism (RFLP) analysis, Amplified Fragment Length Polymorphism (AFLP), and Random Amplified Polymorphic DNA (RADP). All these methods have revealed a high degree of both genetic and antigenic heterogeneity among M. hominis strains 9-12. Although informative, these approaches proved to be quite difficult to

Research paper thumbnail of Phylogenetics of Mycoplasma hominis clinical strains associated with gynecological infections or infertility as disclosed by an expanded multilocus sequence typing scheme

Scientific Reports

To our knowledge, the phylodistribution of M. hominis clinical strains associated with various pa... more To our knowledge, the phylodistribution of M. hominis clinical strains associated with various pathological conditions of the urogenital tract has not been explored hitherto. Here we analyzed the genetic diversity and phylogenetic relationships among 59 M. hominis Tunisian clinical isolates, categorized as gynecological infections-or infertility-associated pathotypes. For this purpose, we developed an expanded multilocus sequence typing (eMLST) scheme, combining the previously reported multilocus sequence typing (MLST) loci (gyrB, tuf, ftsY, uvrA, gap) with a new selected set of putative virulence genes (p120', vaa, lmp1, lmp3, p60), referred herein to as multi-virulence-locus sequence typing (MVLST) loci. In doing so, M. hominis population was segregated into two distinct genetic lineages, which were differentially associated with each pathotype. Such a clear dichotomy was supported by several phylogenetic and population genetic analysis tools. Recombination was found to take place, but not sufficient enough to break down the overall clonal population structure of M. hominis, most likely as a result of purifying selection, which accommodated the most fit clones. In sum, and owing to the eMLST scheme described herein, we provide insightful data on the phylogenetics of M. hominis, arguing for the existence of genetically differentiable urogenital pathotypes. Mycoplasma hominis, which belongs to the Mycoplasmataceae family, in the Mollicutes class, was the first mycoplasma species isolated from humans in 1937 1. It resides, as a commensal, in the lower urogenital tract of healthy persons. Under certain circumstances, M. hominis can cause a variety of genital infections such as bacterial vaginosis, pelvic inflammatory disease, and cervicitis 2. This microorganism seems to be associated with pregnancy complications and neonatal diseases 3. In addition, several studies reported the pathogenic role of M. hominis in infertility 4,5. More interestingly, this species has been linked to a wide range of extragenital infections (septic arthritis, endocarditis, brain abscess), especially in immunocompromised patients 6-8. To better understand the epidemiology and the mode of spread of M. hominis, several molecular typing systems have been developed. These include Pulse-Field Gel Electrophoresis (PFGE), Restriction Fragment Length Polymorphism (RFLP) analysis, Amplified Fragment Length Polymorphism (AFLP), and Random Amplified Polymorphic DNA (RADP). All these methods have revealed a high degree of both genetic and antigenic heterogeneity among M. hominis strains 9-12. Although informative, these approaches proved to be quite difficult to