Implication of the NAD(P)H quinone oxidoreductase (NQO) in increased virulence of OprD mutant Pseudomonas aeruginosa towards human airway epithelium.

Pseudomonas aeruginosa est une des plus importantes bactéries pathogènes opportunistes, occasionnant des infections respiratoires chez les patients atteints de mucoviscidose et de bronchopneumopathie chronique obstructive. Récemment, il a été montré que les souches de P. aeruginosa résistantes aux carbapénèmes par perte de fonction de la porine OprD présentaient une augmentation de fitness et de virulence dans des modèles murins de colonisation digestive, de dissémination à la rate et de pneumonie aiguë. La porine OprD est le canal d’entrée dans la bactérie des carbapénèmes, antibiotiques de dernier recours utilisés dans le traitement des infections à P. aeruginosa résistants. Dans ce travail, à partir d’un modèle d’épithélium des voies aériennes humaines parfaitement différencié et fonctionnel, obtenu grâce à un modèle ex vivo de culture de cellules primaires en interface air-liquide, nous avons démontré pour la première fois chez l’Homme que la pathogénicité accrue de P. aeruginosa OprD mutant, résistant aux carbapénèmes, résultait de sa meilleure croissance pendant l’infection. Cette pathogénicité accrue est la conséquence d’une meilleure résistance de la bactérie à la réponse oxydative antibactérienne de l’épithélium de l’hôte pendant l’infection, dont NQO_Pa, une NAD(P)H quinone oxydoréductase de P. aeruginosa, est un acteur clé.Pseudomonas aeruginosa is one of the most important opportunistic pathogen bacteria responsible for respiratory infections in patients with cystic fibrosis lung disease or chronic obstructive pulmonary disease. Recently, it has been shown that carbapenem-resistant OprD-defective P. aeruginosa strains had increased fitness and virulence in an intestinal colonization, dissemination to the spleen and acute pneumonia murin model. Carbapenems are one of the last resort treatments for resistant P. aeruginosa and use OprD porin as an entryway in the bacteria. In this study, we assessed the virulence of carbapenem-resistant OprD-defective P. aeruginosa on human airway epithelium, using an ex vivo fully differentiated and functional epithelium model obtained from human primary cells cultured in air liquid interface. For the first time, we showed that NAD(P)H quinone oxidoreductase NQO_Pa, was a key player in the response of P. aeruginosa upon the antibacterial oxidative stress of the human airway epithelium, increasing virulence of OprD-defective P. aeruginosa

Current concepts on Pseudomonas aeruginosa interaction with human airway epithelium.

Pseudomonas aeruginosa is a major, but opportunistic, respiratory pathogen, which rarely infects healthy individuals, mainly due to the barrier effect of the human airway epithelium (HAE). This review explores the interaction of P. aeruginosa with HAE and the progression of the infection. The basolateral part of the epithelium, which includes the basolateral membrane of the epithelial cells and the basement membrane, is inaccessible in normal tight epithelia with intact junctions. We highlight how P. aeruginosa exploits weaknesses in the HAE barrier to gain access to the basolateral part of the epithelium. This access is crucial to initiate respiratory infection and is mainly observed in the injured epithelium, in repairing or chronically remodeled epithelium, and during extrusion of senescent cells or cell multiplication during normal epithelium renewal. The subsequent adhesion of the bacteria and cytotoxic action of virulence factors, including the toxins delivered by the type 3 secretion system (T3SS), lead to retractions and cell death. Eventually, P. aeruginosa progressively reaches the basement membrane and propagates radially through the basal part of the epithelium to disseminate using twitching and flagellar motility

Accurate identification of S. pneumoniae using MALDI-TOF mass spectrometry, still a challenge for clinical laboratories?

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Characterization of quinolone resistance mechanisms in Enterobacteriaceae isolated from companion animals in Europe (ComPath II study)

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Nocardiose cutanée chez une patiente immunocompétente A propos d'un cas et revue de la littérature.

International audienceNocardia spp. est responsable d'infections opportunistes chez les patients immunodéprimés, principalement d'infections pulmonaires. Le système nerveux central est la localisation extra-pulmonaire la plus souvent retrouvée. Nous rapportons ici un cas d'infection cutanée à N. brasiliensis chez une patiente immunocompétente, ainsi qu'une revue de la littérature

Copper for the Prevention of Outbreaks of Health Care–Associated Infections in a Long-term Care Facility for Older Adults

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Clonal dissemination of OXA-48-producing Enterobacter cloacae isolates from companion animals in Algeria

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Spread of Klebsiella pneumoniae ST395 non-susceptible to carbapenems and resistant to fluoroquinolones in North-Eastern France

International audienceFluoroquinolones (FQ) are potential treatments to treat infections from extended-spectrum β-lactamase producing-Enterobacteriaceae susceptible to FQ. Due to increasing non-susceptibility to carbapenems among Enterobacteriaceae, we characterized FQ resistance mechanisms in 36 Klebsiella pneumoniae isolates that are non-susceptible to ertapenem in North-Eastern France in 2012 and described the population structure by pulsed field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST). Among them, 36% (13/36) carried a carbapenemase encoding-gene. Decreased expression of the OmpK35 encoding-gene might be considered a major resistance determinant that could explain non-susceptibility to carbapenems. The carbapenemase-producing isolates carried the well-known IncL pOXA48a plasmid. All the K. pneumoniae (36/36) isolates also harbored a fluoroquinolone-resistant (FQ-R) determinant. aac(6')-Ib-cr was the major plasmid-mediated quinolone resistant (PMQR) determinant found in K. pneumoniae (86%, 32/36). The MLST study identified 5 sequence types (STs). The most dominant ST was ST395 (25/36) followed by ST147 (6/36). ST395 strains showed ertapenem minimum inhibitory concentrations (MICs) ranging from 0.75μg/mL to 32μg/mL.K. pneumoniae ST395 did not show enhanced biofilm formation, nor environmental survival, but showed higher chlorhexidine MICs than the ST147 isolates. These findings showed that (i) K. pneumoniae ST395 carrying pOXA-48a has spread in North-Eastern France, (ii) aac(6')-Ib-cr is preponderant in carbapenem non-susceptible K. pneumoniae, (iii) K. pneumoniae ST395 is resistant to chlorhexidine, and (iv) FQ as alternatives to β-lactams to treat ertapenem non-susceptible K. pneumoniae are compromised

A qnrD-Plasmid Promotes Biofilm Formation and Class 1 Integron Gene Cassette Rearrangements in Escherichia coli

International audienceBacteria within biofilms may be exposed to sub-minimum inhibitory concentrations (sub-MICs) of antibiotics. Cell-to-cell contact within biofilms facilitates horizontal gene transfers and favors induction of the SOS response. Altogether, it participates in the emergence of antibiotic resistance. Aminoglycosides at sub-MICs can induce the SOS response through NO accumulation in E. coli carrying the small plasmid with the quinolone resistance qnrD gene (pDIJ09-518a). In this study, we show that in E. coli pDIJ09-518a, the SOS response triggered by sub-MICs of aminoglycosides has important consequences, promoting genetic rearrangement in class 1 integrons and biofilm formation. We found that the integrase expression was increased in E. coli carrying pDIJ09-518a in the presence of tobramycin, which was not observed for the WT isogenic strain that did not carry the qnrD-plasmid. Moreover, we showed that biofilm production was significantly increased in E. coli WT/pDIJ09-518a compared to the WT strain. However, such a higher production was decreased when the Hmp-NO detoxification pathway was fully functional by overexpressing Hmp. Our results showing that a qnrD-plasmid can promote biofilm formation in E. coli and potentiate the acquisition and spread of resistance determinants for other antibiotics complicate the attempts to counteract antibiotic resistance and prevention of biofilm development even further. We anticipate that our findings emphasize the complex challenges that will impact the decisions about antibiotic stewardship, and other decisions related to retaining antibiotics as effective drugs and the development of new drugs

OqxAB and variants of QepA in extended-spectrum β-lactamase-producing Enterobacteriaceae in hospital wastewater in Mali

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