Responses of Pseudomonas aeruginosa to antimicrobials

Abstract

Infections caused by Pseudomonas aeruginosa often are hard to treat; inappropriate chemotherapy readily selects multidrug-resistant P. aeruginosa. This organism can be exposed to a wide range of concentrations of antimicrobials during treatment; learning more about the responses of P. aeruginosa to antimicrobials is therefore important. We review here responses of the bacterium P. aeruginosa upon exposure to antimicrobials at levels below the inhibitory concentration. Carbapenems (e.g., imipenem) have been shown to induce the formation of thicker and more robust biofilms, while fluoroquinolones (e.g., ciprofloxacin) and aminoglycosides (e.g., tobramycin) have been shown to induce biofilm formation. Ciprofloxacin also has been demonstrated to enhance the frequency of mutation to carbapenem resistance. Conversely, although macrolides (e.g., azithromycin) typically are not effective against P. aeruginosa because of the pseudomonal outer-membrane impermeability and efflux, macrolides do lead to a reduction in virulence factor production. Similarly, tetracycline is not very effective against this organism, but is known to induce the type-III secretion system and consequently enhance cytotoxicity of P. aeruginosa in vivo. Of special note are the effects of antibacterials and disinfectants on pseudomonal efflux systems. Sub-inhibitory concentrations of protein synthesis inhibitors (aminoglycosides, tetracycline, chloramphenicol, etc.) induce the MexXY multidrug efflux system. This response is known to be mediated by interference with the translation of the leader peptide PA5471.1, with consequent effects on expression of the PA5471 gene product. Additionally, induction of the MexCD-OprJ multidrug efflux system is observed upon exposure to sub-inhibitory concentrations of disinfectants such as chlorhexidine and benzalkonium. This response is known to be dependent upon the AlgU stress response factor. Altogether, these biological responses of P. aeruginosa provide useful clues for the improvement and optimization of chemotherapy in order to appropriately treat pseudomonal infections while minimizing the emergence of resistance.

Phenotypic and Molecular Detection of Metallo-Beta-Lactamase Genes Among Imipenem Resistant Pseudomonas aeruginosa and Acinetobacter baumannii Strains Isolated From Patients with Burn Injuries

“…Keep it in mind that the resistance genes responsible for antimicrobial resistance are found on conjugative plasmids and that carbapenem and colistin-resistant E. coli may be found in retail meat, if such strains colonise in the human intestinal tract they can transfer the resistance plasmids to other Gram-negative pathogens such as P. aeruginosa and A. baumannii and the consequence is untreatable infections (22). Carbapenem resistance mechanisms in Gram-negative bacilli are associated with resistance to other classes of antibiotics such as penicillins, monobactams and cephalosporins possibly because of parallel resistance mechanisms (23,24). Actually, resistance to carbapenems caused resistance to other valuable antibiotics, which makes the treatment process very difficult.…”

Berberine inhibits the MexXY‑OprM efflux pump to reverse imipenem resistance in a clinical carbapenem‑resistant Pseudomonas aeruginosa isolate in a planktonic state

“…This Gram-negative bacterium may cause a series of infectious diseases, including keratitis, otitis media and bacteremia, in immuno-compromised patients and those in intensive care units with high morbidity and mortality (1). Due to extensive application of antibiotics, an increasing number of P. aeruginosa isolates have been identified to be resistant to various traditional antibacterial agents, including penicillins, fluoroquinolones, aminoglycosides, polymyxins as well as carbapenems, via intrinsic as well as acquired resistance mechanisms (1). One of the essential factors contributing to resistance is associated with efflux pumps, of which four types, namely MexAB-outer membrane protein (Opr)M, MexEF-OprN, MexCD-OprJ and MexXY-OprM, have been widely studied (2).…”

A PhoPQ-Regulated ABC Transporter System Exports Tetracycline in Pseudomonas aeruginosa

“…P. aeruginosa possesses an outer membrane of low permeability, which is about 12 to 100 times lower than that in Escherichia coli (2). The high intrinsic resistance of P. aeruginosa also depends on other mechanisms, such as the intrinsic or induced expression of efflux pumps, particularly the nodulation cell division (RND) systems MexAB-OprM and MexXY-OprM, and adaptive production of drug degradation enzymes, such as AmpC ␤-lactamase (4,5). Also of note, metabolic versatility allows P. aeruginosa to adapt to a wide range of environments, including antibiotic stress (6)(7)(8).…”