Vesicles-mediated resistance to antibiotics in bacteria (original) (raw)
Related papers
Journal of Bacteriology, 1996
Pseudomonas aeruginosa releases membrane vesicles (MVs) filled with periplasmic components during normal growth, and the quantity of these vesicles can be increased by brief exposure to gentamicin. Natural and gentamicin-induced membrane vesicles (n-MVs and g-MVs, respectively) are subtly different from one another, but both contain several important virulence factors, including hydrolytic enzyme factors (J. L. Kadurugamuwa and T. J. Beveridge, J. Bacteriol. 177:3998-4008, 1995). Peptidoglycan hydrolases (autolysins) were detected in both MV types, especially a periplasmic 26-kDa autolysin whose expression has been related to growth phase (Z. Li, A. J. Clarke, and T. J. Beveridge, J. Bacteriol. 178:2479-2488, 1996). g-MVs possessed slightly higher autolysin activity and, at the same time, small quantities of gentamicin. Both MV types hydrolyzed isolated gram-positive and gram-negative murein sacculi and were also capable of hydrolyzing several glycyl peptides. Because the MVs were b...
Antibiotic Resistance Mechanisms of Clinically Important Bacteria
Medicina, 2011
Bacterial resistance to antimicrobial drugs is an increasing health and economic problem. Bacteria may be innate resistant or acquire resistance to one or few classes of antimicrobial agents. Acquired resistance arises from: (i) mutations in cell genes (chromosomal mutation) leading to cross-resistance, (ii) gene transfer from one microorganism to other by plasmids (conjugation or transformation), transposons (conjugation), integrons and bacteriophages (transduction). After a bacterium gains resistance genes to protect itself from various antimicrobial agents, bacteria can use several biochemical types of resistance mechanisms: antibiotic inactivation (interference with cell wall synthesis, e.g., β-lactams and glycopeptide), target modification (inhibition of protein synthesis, e.g., macrolides and tetracyclines; interference with nucleic acid synthesis, e.g., fluoroquinolones and rifampin), altered permeability (changes in outer membrane, e.g., aminoglycosides; new membrane transpo...
Scientific reports, 2017
The β-lactam antibiotic temocillin (6-α-methoxy-ticarcillin) shows stability to most extended spectrum β-lactamases, but is considered inactive against Pseudomonas aeruginosa. Mutations in the MexAB-OprM efflux system, naturally occurring in cystic fibrosis (CF) isolates, have been previously shown to reverse this intrinsic resistance. In the present study, we measured temocillin activity in a large collection (n = 333) of P. aeruginosa CF isolates. 29% of the isolates had MICs ≤ 16 mg/L (proposed clinical breakpoint for temocillin). Mutations were observed in mexA or mexB in isolates for which temocillin MIC was ≤512 mg/L (nucleotide insertions or deletions, premature termination, tandem repeat, nonstop, and missense mutations). A correlation was observed between temocillin MICs and efflux rate of N-phenyl-1-naphthylamine (MexAB-OprM fluorescent substrate) and extracellular exopolysaccharide abundance (contributing to a mucoid phenotype). OpdK or OpdF anion-specific porins expressi...
European Journal of Biochemistry, 1989
A pair of strains of Pseudomonas aeruginosa (3-Pre : cefsulodin-sensitive, inducible /?-lactamase ; and 3-Post: cefsulodin-resistant, elevated fl-lactamase, derived from 3-Pre by subculture in the presence of cefsulodin) were taken as representative of the class of bacteria resistant to third-generation cephalosporins due to elevated synthesis of the normally inducible, chromosomally encoded j-lactamase. These two strains were used to differentiate between 'trapping' and 'hydrolytic' mechanisms of cefsulodin resistance by (a) measuring the outer-membrane permeabilities to cefsulodin, (b) measuring the kinetics of cefsulodin hydrolysis and the stoichiometry of cefsulodin trapping by the periplasmic b-lactamase, and (c) comparing the predictions of the trapping and hydrolysis hypotheses with the minimum inhibitory concentrations (MIC) of cefsulodin. The MIC of cefsulodin for strains 3-Pre and 3-Post were 2.35 pM (1.25 pg ml-') and 37.6 pM (20.0 pg ml-') respectively. The permeability parameter for cefsulodin of the outer membrane of the resistant strain was 0.0034 cm3 min-' mg dry mass-', so the flux of cefsulodin across its outer membrane at the MIC was calculated to be 0.120 nmol min-' mg dry mass-'.
Staphylococcus aureus Extracellular Vesicles Carry Biologically Active -Lactamase
Antimicrobial Agents and Chemotherapy, 2013
ABSTRACTGram-positive bacteria naturally produce extracellular vesicles. However, little is known regarding the functions of Gram-positive bacterial extracellular vesicles, especially in the bacterial community. Here, we investigated the role ofStaphylococcus aureusextracellular vesicles in interbacterial communication to cope with antibiotic stress. We found thatS. aureusliberated BlaZ, a β-lactamase protein, via extracellular vesicles. These extracellular vesicles enabled other ampicillin-susceptible Gram-negative and Gram-positive bacteria to survive in the presence of ampicillin. However,S. aureusextracellular vesicles did not mediate the survival of tetracycline-, chloramphenicol-, or kanamycin-susceptible bacteria. Moreover,S. aureusextracellular vesicles did not contain theblaZgene. In addition, the heat-treatedS. aureusextracellular vesicles did not mediate the survival of ampicillin-susceptible bacteria. The β-lactamase activities ofS. aureussoluble and extracellular vesicl...
Staphylococcus aureus Extracellular Vesicles Carry Biologically Active β-Lactamase
Antimicrobial Agents and Chemotherapy, 2013
Gram-positive bacteria naturally produce extracellular vesicles. However, little is known regarding the functions of Gram-positive bacterial extracellular vesicles, especially in the bacterial community. Here, we investigated the role of Staphylococcus aureus extracellular vesicles in interbacterial communication to cope with antibiotic stress. We found that S. aureus liberated BlaZ, a -lactamase protein, via extracellular vesicles. These extracellular vesicles enabled other ampicillin-susceptible Gram-negative and Gram-positive bacteria to survive in the presence of ampicillin. However, S. aureus extracellular vesicles did not mediate the survival of tetracycline-, chloramphenicol-, or kanamycin-susceptible bacteria. Moreover, S. aureus extracellular vesicles did not contain the blaZ gene. In addition, the heat-treated S. aureus extracellular vesicles did not mediate the survival of ampicillinsusceptible bacteria. The -lactamase activities of S. aureus soluble and extracellular vesicle-associated BlaZ were similar, but only the extracellular vesicle-associated BlaZ was resistant to protease digestion, which suggests that the enzymatic activity of BlaZ in extracellular vesicles is largely protected by the vesicle structure. Our observations provide evidence of the important role of S. aureus extracellular vesicles in antibiotic resistance, which allows the polymicrobial community to continue to evolve and prosper against antibiotics.
Journal of Antimicrobial Chemotherapy, 2013
Objectives: Group A streptococci (GAS) cause, among other infections, pharyngotonsillitis in children. The species is frequently localized with the Gram-negative respiratory pathogens non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis, which both produce outer membrane vesicles (OMVs). The aim of this study was to investigate whether OMVs isolated from NTHi contain functional b-lactamase and whether the OMVs hydrolyse amoxicillin and thus protect GAS from killing by the antibiotic. Methods: The antibiotic susceptibility of isolates was determined using the Etest. The resistance genes bla TEM-1 (encoding NTHi b-lactamase), bro-1 (encoding M. catarrhalis b-lactamase) and ftsI (encoding NTHi penicillin-binding protein 3) were searched for by PCR, followed by sequencing. OMVs were isolated by ultracentrifugation and the presence of b-lactamase was detected by western blots including specific rabbit polyclonal antibodies. The chromogenic substrate nitrocefin was used to quantify and compare the b-lactamase enzyme activity in the OMVs. The hydrolysis of amoxicillin by b-lactamase was estimated by an agar diffusion method. Results: We showed that OMVs released from b-lactam-resistant M. catarrhalis and NTHi contain functional b-lactamase that hydrolyses amoxicillin and protects GAS from killing by amoxicillin. Conclusions: This is the first report of the presence of b-lactamase in NTHi OMVs. We suggest that OMV-derived b-lactamase from coinfecting pathogens such as NTHi and M. catarrhalis may contribute to the occasional treatment failures seen in GAS tonsillitis.
What's new in antibiotic resistance? Focus on beta-lactamases
Drug Resistance Updates, 2006
In gram-negative bacteria, beta-lactamases are the most important mechanism of resistance to beta-lactam antibiotics. Currently, the beta-lactamases receiving the most attention are the extended-spectrum beta-lactamases (ESBLs), inhibitor-resistant beta-lactamases and carbapenemases. When found in Escherichia coli and Klebsiella spp., ESBLs confer resistance to extended-spectrum cephalosporins, such as ceftazidime, cefotaxime and cefepime. Hence, ESBLs limit the choice of beta-lactam therapy to carbapenems. A worrisome trend is the increasing number of pathogens found in isolates from patients in the community that possess ESBLs. It is equally distressing that carbapenemases (serine and metallo-beta-lactamases) are being found in many of the same bacteria that harbor ESBLs, for example Klebsiella pneumoniae. Despite many years studying beta-lactamases, important clinical and scientific questions still remain.
Folia Histochemica et Cytobiologica, 2008
Since about twenty years, following the introduction into therapeutic of news β-lactam antibiotics (broad-spectrum cephalosporins, monobactams and carbapenems), a very significant number of new β-lactamases appeared. These enzymes confer to the bacteria which put them, the means of resisting new molecules. The genetic events involved in this evolution are of two types: evolution of old enzymes by mutation and especially appearance of new genes coming for some, from bacteria of the environment. Numerous mechanisms of enzymatic resistance to the carbapenems have been described in Pseudomonas aeruginosa. The important mechanism of inactivation carbapenems is production variety of b-lactam hydrolysing enzymes associated to carbapenemases. The metallo-β-enzymes (IMP, VIM, SPM, GIM types) are the most clinically significant carbapenemases. P. aeruginosa posses MBLs and seem to have acquired them through transmissible genetic elements (plasmids or transposons associated with integron) and can be transmission to other bacteria. They have reported worldwide but mostly from South East Asia and Europe. The enzymes, belonging to the molecular class B family, are the most worrisome of all β-lactamases because they confer resistance to carbapenems and all the β-lactams (with the exception of aztreonam) and usually to aminoglycosides and quinolones. The dissemination of MBLs genes is thought to be driven by regional consumption of extended-spectrum antibiotics (e.g. cephalosporins and carbapenems), and therefore care must be taken that these drugs are not used unnecessarily.