Carbapenem-resistance mechanisms of multidrug-resistant Pseudomonas aeruginosa

Abstract

Clonal dissemination of multidrug-resistant Pseudomonas aeruginosa (MDRPA) is a major concern worldwide. The aim of this study was to explore the mechanisms leading to the carbapenem resistance of an MDRPA clone. Isolates were obtained from a surgical wound, sputum, urine and a blood culture. Pulsed-field gel electrophoresis (PFGE) showed high genomic homogeneity of these isolates and confirmed the circulation of an endemic clone belonging to serotype O4. Outer membrane protein (OMP) bands were visualized by SDS-PAGE, meropenem accumulation was measured in a bioassay and integrons were detected by PCR. Efflux pumps were studied for several antimicrobial agents and synergic combinations thereof in the presence or absence of both carbonyl cyanide m-chlorophenylhydrazone (CCCP) and Phe-Arg-bnaphthylamide (PAbN) at final concentrations of 10 and 40 mg l "1 , respectively. On OMP electrophoretic profiles, MDRPA showed a reduction of outer membrane porin D (OprD) and PCR demonstrated the presence of a class 1 integron with a cassette encoding aminoglycoside adenyltransferase B (aadB). Meropenem accumulation was slightly higher in bacilli than in the filamentous cells that formed in the presence of antibiotics. Overexpression of the efflux pump MexAB-OprM and a functional MexXY-OprM were detected in all isolates.

Efflux MexAB-Mediated Resistance in Multidrug and Pan-Drug Resistant Strains of Pseudomonas aeruginosa Isolated From Patients With Burn and Wound Infections

“…Their results showed an overexpression of the MexAB-OprM efflux pump, and a functional MexXY-OprM was detected in all isolates (23).…”

<p>Molecular Mechanisms and Epidemiology of Carbapenem-Resistant <em>Escherichia coli</em> Isolated from Chinese Patients During 2002–2017</p>

“…7, 8 The mechanisms of carbapenem resistance are strongly associated with carbapenemase production (acquisition of carbapenemase genes), combination of porin loss with extended-spectrum β-lactamases (ESBLs) and the overexpression of efflux pumps. 9,10 Several studies have reported that acquired carbapenemase isolates might cause hospital outbreaks and become endemic in healthcare settings. 11,12 Globally predominant carbapenemases include KPC, NDM, VIM, IMP, and OXA, which are encoded by bla KPC , bla NDM , bla VIM , bla IMP , and bla OXA genes present in both the plasmid and the chromosome.…”

Sodium colistimethate loaded lipid nanocarriers for the treatment of Pseudomonas aeruginosa infections associated with cystic fibrosis

“…Among the pathogens that affect the CF patients, Pseudomonas aeruginosa (PA) is the most prevalent, but the treatment of its infections is often difficult due to the wide range of antimicrobial resistance of this species. This resistance to antimicrobials is a well documented phenomenon due to several molecular mechanisms such as the restricted outer membrane permeability, the presence of integron, insertion sequences, and the biosynthesis of degrading-enzymes (Fuste et al, 2013;Ruiz-Martinez et al, 2011a;Ruiz-Martinez et al, 2011b). P. aeruginosa infections usually start as an acute infection that finally becomes chronic.…”