Staphylococcus aureus biofilms: Structures, antibiotic resistance, inhibition, and vaccines (original) (raw)

Staphylococcus aureus Biofilm: Morphology, Genetics, Pathogenesis and Treatment Strategies

International Journal of Environmental Research and Public Health, 2021

Staphylococcus aureus is a nosocomial bacterium causing different infectious diseases, ranging from skin and soft tissue infections to more serious and life-threatening infections such as septicaemia. S. aureus forms a complex structure of extracellular polymeric biofilm that provides a fully secured and functional environment for the formation of microcolonies, their sustenance and recolonization of sessile cells after its dispersal. Staphylococcus aureus biofilm protects the cells against hostile conditions, i.e., changes in temperature, limitations or deprivation of nutrients and dehydration, and, more importantly, protects the cells against antibacterial drugs. Drugs are increasingly becoming partially or fully inactive against S. aureus as they are either less penetrable or totally impenetrable due to the presence of biofilms surrounding the bacterial cells. Other factors, such as evasion of innate host immune system, genome plasticity and adaptability through gene evolution an...

Staphylococcus aureus Biofilms and their Impact on the Medical Field

The Rise of Virulence and Antibiotic Resistance in <i>Staphylococcus aureus</i>, 2017

Despite the discovery of antibiotics, the battle against bacteria is so far in their favor, specifically because bugs are able to develop a superstructure named biofilm, to resist and to survive in the environment. Nosocomial infections, a major health problem, are due at 80% to biofilm-associated infection, and Staphylococcus aureus is the leading bacteria species in this domain. Moreover, the antimicrobial resistance of this bacterial community is accentuated when it is formed by superbugs such as methicillin-resistant S. aureus (MRSA). In this chapter, the mechanism and the physiology of S. aureus biofilm as well as their consequences in the clinical domains are described. To complete the vision on S. aureus biofilms, some "anti-biofilm" strategies will be highlighted.

Human methicillin-sensitive Staphylococcus aureus biofilms: potential associations with antibiotic resistance persistence and surface polysaccharide antigens

Journal of Basic Microbiology, 2013

The development of persistent antibiotic resistance by human methicillin-sensitive Staphylococcus aureus (MSSA) strains and substantial association with poly-N-acetyl glucosamine (PNAG) in biofilms is reported in this investigation. Sixteen of 31 MSSA strains under study were found to have developed resistance to one or more antibiotics, with four strains, two of which did not produce biofilms, showing resistance to cefoxitin, undetectable by mecA amplification. Antibiotic resistance displayed by 13/14 biofilm-forming S. aureus isolates remained persistent for 4 weeks prior to reverting back to the original antibiotic susceptibility, prompting a suggestion of determining antibiograms for clinical S. aureus isolates subcultured from biofilms developed in vitro as well as planktonic subcultures prepared from the site of infection. While there was correlation of antibiotic resistance with biofilm formation confirming previous reports, this is the first time that persistence of the biofilm-associated antibiotic resistance by S. aureus as planktonic cells is reported. Among the two methods used for assessment of biofilm formation, the tissue culture plate (TCP) method revealed that almost all strains were strong or moderate biofilm producers whereas only 19/31 strains were biofilm producers using the Congo Red agar (CRA) method indicating the superiority of the TCP method in detecting biofilm producers. We also observed no association between biofilm formation and major capsule types. However, substantial, although not absolute, association of biofilm formation with PNAG was observed, warranting continued identification of additional surface-associated polysaccharide and/or protein antigens associated with biofilm formation for development of an effective vaccine against S. aureus infections regardless of capsular phenotype.

A Study of Biofilm Production in Staphyloccus Aureus

2014

Aims and objectives: (1) To detect biofilm formation in clinical isolates of Staphylococcus aureus. (2) To know the antimicrobial resistance pattern of the isolates and correlation with biofilm production. Methodology: The present study was done to detect biofilm formation in 50 clinical isolates of Staphylococcus aureus from blood and indwelling devices. For detection of biofilm formation, the clinical isolates were screened by Modified Tissue Culture Plate method (MTCP) and Tube Method (TM).Antibiotic susceptibility of the isolates was determined by using KirbyBauer disc diffusion method. Results: Out of 50 isolates of Staphylococcus aureus, 46% were biofilm positive by MTCP and 38% by TM. The biofilm producers were multi drug resistant as compared to the non producers. Interpretation: The effective control for staphylococcal infections will require a concerted effort to develop therapeutic agents that target the biofilm phenotype.

Genotypically Different Clones of Staphylococcus aureus Are Diverse in the Antimicrobial Susceptibility Patterns and Biofilm Formations

BioMed Research International, 2013

This study evaluated whether genotypically different clinical isolates of S. aureus have similar susceptibilities to individual antibiotics. It further aims to check the impact of biofilm on the in vitro activity of vancomycin, daptomycin, linezolid, and tigecycline against S. aureus clones. The study used a total of 60 different clinical MSSA and MRSA isolates. Susceptibilities were performed in planktonic cultures by macrobroth dilution and epsilon-test (E test) system. Biofilm production was determined using an adherent plate assay. The efficacy of antimicrobial activities against biofilms formation was checked using confocal laser scanning microscopy (CLSM). The study found that similar and different spa, MLST, and SCCmec types displayed high variation in their susceptibilities to antibiotics with tigecycline and daptomycin being the most effective. The biofilms were found resistant to high concentrations of most antibiotics tested with daptomycin being the most effective drug used in adhesive biofilms. A considerable difference exists among similar and various clone types against antibiotics tested. This variation could have contributed to the degree of virulence even within the same clonal genotype and enhanced heterogeneity in the infection potential. Thus, the development of a rapid and precise identification profile for each clone in human infections is important.

No Correlation between Biofilm-Forming Capacity and Antibiotic Resistance in Environmental Staphylococcus spp.: In Vitro Results

Pathogens, 2022

The production of biofilms is a critical factor in facilitating the survival of Staphylococcus spp. in vivo and in protecting against various environmental noxa. The possible relationship between the antibiotic-resistant phenotype and biofilm-forming capacity has raised considerable interest. The purpose of the study was to assess the interdependence between biofilm-forming capacity and the antibiotic-resistant phenotype in 299 Staphylococcus spp. (S. aureus n = 143, non-aureus staphylococci [NAS] n = 156) of environmental origin. Antimicrobial susceptibility testing and detection of methicillin resistance (MR) was performed. The capacity of isolates to produce biofilms was assessed using Congo red agar (CRA) plates and a crystal violet microtiter-plate-based (CV-MTP) method. MR was identified in 46.9% of S. aureus and 53.8% of NAS isolates (p > 0.05), with resistance to most commonly used drugs being significantly higher in MR isolates compared to methicillin-susceptible isolates. Resistance rates were highest for clindamycin (57.9%), erythromycin (52.2%) and trimethoprim-sulfamethoxazole (51.1%), while susceptibility was retained for most last-resort drugs. Based on the CRA plates, biofilm was produced by 30.8% of S. aureus and 44.9% of NAS (p = 0.014), while based on the CV-MTP method, 51.7% of S. aureus and 62.8% of NAS were identified as strong biofilm producers, respectively (mean OD570 values: S. aureus: 0.779±0.471 vs. NAS: 1.053±0.551; p < 0.001). No significant differences in biofilm formation were observed based on MR (susceptible: 0.824 ± 0.325 vs. resistant: 0.896 ± 0.367; p = 0.101). However, pronounced differences in biofilm formation were identified based on rifampicin susceptibility (S: 0.784 ± 0.281 vs. R: 1.239 ± 0.286; p = 0.011). The mechanistic understanding of the mechanisms Staphylococcus spp. use to withstand harsh environmental and in vivo conditions is crucial to appropriately address the therapy and eradication of these pathogens.

Level of biofilm production by Staphylococcus aureus isolates is critical for resistance against most but not all antimicrobial drugs

Pakistan Journal of Medical Sciences

Background and Objective: Staphylococcal biofilms cause a wide range of acute and chronic infections, both in hospital and community settings across the world. This study explores biofilm forming propensity among Staphylococcus aureus clinical isolates from Faisalabad, Pakistan and their association with antimicrobial drug resistance. Methods: The study was conducted during July to December 2020. The biofilm forming ability of S. aureus isolates was assessed by crystal violet staining in 96 well plates. Antimicrobial susceptibility was determined by disk diffusion method against ten antimicrobials representing whole spectrum of antimicrobial drugs. Results: All the isolates (n=22) produced biofilm; 14 (63.6%) were strong, and 8 (36.4%) moderate biofilm producers. Comparative data were obtained for moderate and strong biofilm producers. Increased biofilm production did not affect azithromycin, clindamycin and mupirocin. However, stronger biofilm production significantly increased res...

Comparison of virulence factors and biofilm formation among Staphylococcus aureus strains isolated from human and bovine infections

Microbial pathogenesis, 2015

The aim of this study was to find different prevalence of genes involved in the biofilm formation process and to assess the phenotypic and genotypic markers of biofilm formation among Staphylococcus aureus strains isolated from human and bovine infections. In this study, 215 S. aureus strains were collected from human and dairy cow's infections. The biofilm forming capacity of the strains was evaluated using a colorimetric microtiter plate assay. The genes encoding microbial surface components, recognizing adhesive matrix molecules (MSCRAMMs) (ebpS, eno, fib, fnbA, fnbB, cna and bap), and the intracellular adhesion (ica) genes (icaA, and icaD) were targeted by polymerase chain reaction (PCR)-based method. Approximately 70% of the isolates produced biofilm. Among these, 59.3% were producers of weakly adherent biofilms while 34.8% and 5.8% produced moderate and strong biofilms, respectively. The most prevalent gene was icaD found in 88.4% of the isolates, followed by icaA, fib and...

Staphylococcus aureus clinical isolates: antibiotic susceptibility, molecular characteristics, and ability to form biofilm

Periodic monitoring of Staphylococcus aureus characteristics in a locality is imperative as their drug-resistant variants cause treatment problem. In this study, antibiograms, prevalence of toxin genes (sea-see, seg-ser, seu, tsst-1, eta, etb, and etd), PFGE types, accessory gene regulator (agr) groups, and ability to form biofilm of 92 S. aureus Thailand clinical isolates were investigated. They were classified into 10 drug groups: groups 1-7 (56 isolates) were methicillin resistant (MRSA) and 8-10 (36 isolates) were methicillin sensitive (MSSA). One isolate did not have any toxin gene, 4 isolates carried one toxin gene (seq), and 87 isolates had two or more toxin genes. No isolate had see, etb, or tsst-1; six isolates had eta or etd. Combined seg-sei-sem-sen-seo of the highly prevalent egc locus was 26.1%. The seb, sec, sel, seu, and eta associated significantly with MSSA; sek was more in MRSA. The sek-seq association was 52.17% while combined sed-sej was not found. Twenty-three PFGE types were revealed, no association of toxin genes with PFGE types. All four agr groups were present; agr group 1 was predominant (58.70%) but agr group 2 strains carried more toxin genes and were more frequent toxin producers. Biofilm formation was found in 72.83% of the isolates but there was no association with antibiograms. This study provides insight information on molecular and phenotypic markers of Thailand S. aureus clinical isolates which should be useful for future active surveillance that aimed to control a spread of existing antimicrobial resistant bacteria and early recognition of a newly emerged variant. BioMed Research International cytokines and T-cell stimulating factors leading to toxic shock syndrome which may be fatal [8, 9]. The enterotoxicity and superantigenicity are distinct properties of the toxin molecule [6]. SEs are classified into two types based on their emetic activity in the toxin fed modeled primate. Toxins that induce vomiting in the primate are placed in the classical SE type while those that lack the emetic activity or have not been tested are allocated in the SE-like (SEls) type [10, 11]. Members of the classical SEs are SEA-SEE and the more recently recognized SEG, SEH, SEI, SER, SES, and SET. The SEls members include SElJ, SElK, SElL, SElM, SElN, SElO, SElP, SElQ, SElU, SElU2 or SEW, and SElV [11]. The staphylococcal enterotoxin F (SEF) which lacks emetic activity but is associated with toxic shock syndrome is presently called toxic shock syndrome toxin-1 (TSST-1) [12]. The SEs and the TSST-1 as well as the bacterial resistance to drugs are encoded by genes on the mobile genetic elements including prophages, plasmids, pathogenicity islands, genomic islands, and antibiotic resistance cassette [13]; thus they are transmitted horizontally rather easily. Expression of S. aureus virulence factors and metabolism of metabolic pathways during growth are coordinated/regulated by a quorumsensing operon named accessory gene regulator (agr) [14, 15]. Based on the amino acid sequence polymorphisms of the agr-encoding autoinducing peptides and their responding receptors, S. aureus strains can be divided into four major agr groups (groups 1-4) [16]. During the last five decades, S. aureus clones that resist methicillin (methicillin-resistant S. aureus, MRSA) disseminated and caused medical and public health problem worldwide [17, 18]. These strains are not only resistant to methicillin, but also resistant to all other-lactams, such as cephalosporin [18, 19]. In Thailand, MRSA infections were reported from 23 hospitals from 1988 to 1998 [20, 21]. The proportions of MRSA to MSSA in the northeast, central, and southern regions of the country during the studied period increased from 11 to 23.4%, 16 to 30.5%, and 21 to 30.3%, respectively [22]. Moreover, methicillin-resistant S. aureus with reduced susceptibility to vancomycin was recognized [23]. However, data on genotypic characteristics and other attributes of the S. aureus isolates in Thailand are relatively rare. Therefore, this study investigated the prevalence of virulence toxin genes coding for enterotoxins (sea-see, seg-ser, and seu), toxic shock syndrome toxin-1 (tsst-1), and exfoliative toxins (eta, etb, and etd) among S. aureus Thailand clinical isolates. Molecular diversity of the isolates regarding their endonuclease-restricted patterns of genomic DNA (PFGE), agr types, and antimicrobial susceptibility as well as their ability to produce biofilm were also investigated.