0000000000374360
AUTHOR
Katy Jeannot
The Efflux Pump MexXY/OprM Contributes to the Tolerance and Acquired Resistance of Pseudomonas aeruginosa to Colistin
The intrinsic resistance of Pseudomonas aeruginosa to polymyxins in part relies on the addition of 4-amino-4-deoxy-l-arabinose (Ara4N) molecules to the lipid A of lipopolysaccharide (LPS), through induction of operon arnBCADTEF-ugd (arn) expression. As demonstrated previously, at least three two-component regulatory systems (PmrAB, ParRS, and CprRS) are able to upregulate this operon when bacteria are exposed to colistin. In the present study, gene deletion experiments with the bioluminescent strain PAO1::lux showed that ParRS is a key element in the tolerance of P. aeruginosa to this last-resort antibiotic (i.e., resistance to early drug killing). Other loci of the ParR regulon, such as th…
Mechanisms of Resistance to Ceftolozane/Tazobactam in Pseudomonas aeruginosa : Results of the GERPA Multicenter Study
ABSTRACT Resistance mechanisms of Pseudomonas aeruginosa to ceftolozane/tazobactam (C/T) were assessed on a collection of 420 nonredundant strains nonsusceptible to ceftazidime (MIC > 8 μg/ml) and/or imipenem (>4 μg/ml), collected by 36 French hospital laboratories over a one-month period (the GERPA study). Rates of C/T resistance (MIC > 4/4 μg/ml) were equal to 10% in this population (42/420 strains), and 23.2% (26/112) among the isolates resistant to both ceftazidime and imipenem. A first group of 21 strains (50%) was found to harbor various extended-spectrum β-lactamases (1 OXA-14; 2 OXA-19; 1 OXA-35; 1 GES-9; and 3 PER-1), carbapenemases (2 GES-5; 1 IMP-8; and 8 VIM-2), or both (1 VIM-2…
The unusual structure of Ruminococcin C1 antimicrobial peptide confers clinical properties.
The emergence of superbugs developing resistance to antibiotics and the resurgence of microbial infections have led scientists to start an antimicrobial arms race. In this context, we have previously identified an active RiPP, the Ruminococcin C1, naturally produced by Ruminococcus gnavus E1, a symbiont of the healthy human intestinal microbiota. This RiPP, subclassified as a sactipeptide, requires the host digestive system to become active against pathogenic Clostridia and multidrug-resistant strains. Here, we report its unique compact structure on the basis of four intramolecular thioether bridges introduced post-translationally by a specific radical-SAM sactisynthase. This structure con…
Coordinate overexpression of two RND efflux systems, ParXY and TtgABC , is responsible for multidrug resistance in Pseudomonas putida
Resistance Nodulation cell Division (RND) efflux pumps are known to contribute to the tolerance of Pseudomonas putida to aromatic hydrocarbons, but their role in antibiotic resistance has not been fully elucidated. In this study, two types of single-step multidrug-resistant (MDR) mutants were selected in vitro from reference strain KT2440. Mutants of the first type were more resistant to fluoroquinolones and β-lactams except imipenem, and overproduced the efflux system TtgABC as a result of mutations occurring in regulator TtgR. In addition to TtgABC, mutants of the second type such as HPG-5 were found to upregulate a novel RND pump, dubbed ParXY/TtgC, which accommodates cefepim, fluoroquin…
Performance of disc diffusion, MIC gradient tests and Vitek 2 for ceftolozane/tazobactam and ceftazidime/avibactam susceptibility testing of Pseudomonas aeruginosa
AbstractObjectivesTo assess performance of disc diffusion, gradient tests and Vitek 2 system to determine the susceptibility of clinical Pseudomonas aeruginosa strains to ceftolozane/tazobactam (C/T) and ceftazidime/avibactam (CZA).MethodsTwo-hundred non-duplicate P. aeruginosa strains isolated by 47 French medical laboratories were selected to cover a wide range of C/T and CZA MICs. Performance of C/T disc (30/10 μg, Bio-Rad), CZA discs (10/4 μg) (Thermo Fisher and Bio-Rad), C/T and CZA gradient tests (Etest, BioMérieux; MIC Test Strip, Liofilchem), and AST-XN12 card of Vitek 2 system (BioMérieux) were compared with a broth microdilution (BMD) method (Thermo Fisher). MIC and disc results w…
Acquisition of Class C β-Lactamase PAC-1 by Sequence Type 644 Strains of Pseudomonas aeruginosa
Four sequence type 664 (ST664) (serotype O:5) strains of Pseudomonas aeruginosa that were highly resistant to antibiotics, including ceftolozane-tazobactam and ceftazidime-avibactam, but were susceptible to colistin were found to harbor the gene encoding the rare class C β-lactamase PAC-1 on a chromosomally located Tn 1721 -like transposon. The bla PAC-1 gene was associated with the 16S rRNA methylase determinant rmtF2 , which confers pan-aminoglycoside resistance.
Production of Norspermidine Contributes to Aminoglycoside Resistance in pmrAB Mutants of Pseudomonas aeruginosa
Emergence of resistance to polymyxins in Pseudomonas aeruginosa is mainly due to mutations in two-components systems, that promote addition of 4-amino-4-deoxy-L-arabinose to the lipopolysaccharide (LPS) through upregulation of operon arnBCADTEF-ugd (arn) expression. Here, we demonstrate that mutations occurring in different domains of histidine kinase PmrB or in response regulator PmrA result in coresistance to aminoglycosides and colistin. All seventeen clinical strains tested exhibiting such a cross-resistance phenotype were found to be pmrAB mutants. As shown by gene deletion experiments, the decreased susceptibility of the mutants to aminoglycosides was independent from operon arn but r…