Antibacterial-ResistantPseudomonas aeruginosa: Clinical Impact and Complex Regulation of Chromosomally Encoded Resistance Mechanisms

Abstract

SUMMARY Treatment of infectious diseases becomes more challenging with each passing year. This is especially true for infections caused by the opportunistic pathogen Pseudomonas aeruginosa, with its ability to rapidly develop resistance to multiple classes of antibiotics. Although the import of resistance mechanisms on mobile genetic elements is always a concern, the most difficult challenge we face with P. aeruginosa is its ability to rapidly develop resistance during the course of treating an infection. The chromosomally encoded AmpC cephalosporinase, the outer membrane porin OprD, and the multidrug efflux pumps are particularly relevant to this therapeutic challenge. The discussion presented in this review highlights the clinical significance of these chromosomally encoded resistance mechanisms, as well as the complex mechanisms/pathways by which P. aeruginosa regulates their expression. Although a great deal of knowledge has been gained toward understanding the regulation of AmpC, OprD, and efflux pumps in P. aeruginosa, it is clear that we have much to learn about how this resourceful pathogen coregulates different resistance mechanisms to overcome the antibacterial challenges it faces.

Rapid evolution of generalized resistance mechanisms can constrain the efficacy of phage–antibiotic treatments

“…It is considered to be a leading source of nosocomial infections and is commonly linked with chronic diseases such as cystic fibrosis, where it is a major cause of morbidity and mortality (J. C. Davies, 2002). Pseudomonas aeruginosa infections are often difficult to treat because of low antibiotic susceptibility and the emergence of multidrug‐resistant strains (Lister, Wolter, & Hanson, 2009). We set up four treatments where we evolved P. aeruginosa in the presence of gentamycin, phage 14/1 or both for 15 days under highly controlled laboratory conditions ( N  = 5).…”

The race for antimicrobials in the multidrug resistance era

“…Indeed, a devastating report by the World Health Organization (WHO) warned of the exponential increase in the death rate in patients infected with multidrug‐resistant pathogenic bacteria, fundamentally due to the ability of these strains to become resistant to the last lines of antibiotics (Taconelli and Magrini, 2017) (http://www.who.int/medicines/publications/WHO-PPL-Short_Summary_25Feb-ET_NM_WHO.pdf?ua=1). Examples include Pseudomonas aeruginosa or Acinetobacter baumannii strains that are responsible for multiple nosocomial diseases and are resistant to β‐lactams, such as carbapenems or third‐generation cephalosporins (Lister et al ., 2009; Vila and Pachon, 2011). Intensification of financial incentives, new regulatory criteria for drug approvals and the identification of new therapeutic targets for antibiotic discovery are actions to be taken to overcome this threat to public health (Laxminarayan, 2014).…”

Prevalence of antibiotic resistance and blaIMP-1 gene among Pseudomonas aeruginosa strains isolated from burn and urinary tract infections in Isfahan, central Iran

“…8,9 However, a large proportion of uncontrolled antibiotic usage has subsidized to the development of resistance in P. aeruginosa strains. 8,9 P. aeruginosa strains exhibits the highest levels of resistance against fluoroquinolones, beta-lactams, penicilins, tetracyclines, carbapenems, aminoglycosides, macrolides and other types of antimicrobial agents. High levels of antibiotic resistance in the P. aeruginosa isolates of UTIs and BIs have been reported previously.…”

“…7 Resistant P. aeruginosa strains cause more severe clinical diseases which are mainly difficult to treatment with routine antibiotics. 8,9 Treatment of UTIs and BIs caused by this bacterium is often started empirically and therapy is based on information determined from the antimicrobial resistance pattern. 8,9 However, a large proportion of uncontrolled antibiotic usage has subsidized to the development of resistance in P. aeruginosa strains.…”

“…8,9 Treatment of UTIs and BIs caused by this bacterium is often started empirically and therapy is based on information determined from the antimicrobial resistance pattern. 8,9 However, a large proportion of uncontrolled antibiotic usage has subsidized to the development of resistance in P. aeruginosa strains. 8,9 P. aeruginosa strains exhibits the highest levels of resistance against fluoroquinolones, beta-lactams, penicilins, tetracyclines, carbapenems, aminoglycosides, macrolides and other types of antimicrobial agents.…”