Interplay between Colistin Resistance, Virulence and Fitness in Acinetobacter baumannii

Abstract

Acinetobacter baumannii is an important opportunistic nosocomial pathogen often resistant to multiple antibiotics classes. Colistin, an “old” antibiotic, is now considered a last-line treatment option for extremely resistant isolates. In the meantime, resistance to colistin has been reported in clinical A. baumannii strains. Colistin is a cationic peptide that disrupts the outer membrane (OM) of Gram-negative bacteria. Colistin resistance is primarily due to post-translational modification or loss of the lipopolysaccharide (LPS) molecules inserted into the outer leaflet of the OM. LPS modification prevents the binding of polymyxin to the bacterial surface and may lead to alterations in bacterial virulence. Antimicrobial pressure drives the evolution of antimicrobial resistance and resistance is often associated with a reduced bacterial fitness. Therefore, the alterations in LPS may induce changes in the fitness of A. baumannii. However, compensatory mutations in clinical A. baumannii may ameliorate the cost of resistance and may play an important role in the dissemination of colistin-resistant A. baumannii isolates. The focus of this review is to summarize the colistin resistance mechanisms, and understand their impact on the fitness and virulence of bacteria and on the dissemination of colistin-resistant A. baumannii strains.

Phenotypic changes associated with Colistin resistance due to Lipopolysaccharide loss in Acinetobacter baumannii

“…The results presented here also indicate that mutations in the PmrAB system (strains CS01 and CR17) can affect biofilm formation, surface motility and growth under iron limitation, but not susceptibility to different disinfectants. Our group and others have previously demonstrated that A. baumannii strains with mutations in the PmrAB system (including strains CS01 and CR17 used in the present study) demonstrate reduced fitness and virulence [ 28 , 35-38 ]. It is important to note, however, that separate studies assessing fitness in PmrAB mutant strains demonstrated no changes in fitness compared to parental strains [ 35 , 39 , 40 ].…”

Colistin and its role in the Era of antibiotic resistance: an extended review (2000–2019)

“…In A. baumannii, eighteen putative efflux transporters were found upregulated in response to the physiological level of NaCl, resulting in increased tolerance to various antibiotics, including colistin [67].…”

“…Furthermore, Da Silva et al [67] revealed that the use of efflux inhibitors, such as carbonyl cyanide 3chlorophenylhydrazone (CCCP) could decrease the resistance pattern of colistin in A. baumannii, K. pneumoniae, P. aeruginosa, and Stenotrophomonas maltophilia, strongly suggesting the involvement of efflux pumps in the colistin resistance phenotype.…”

Bacteria-Host Crosstalk: Sensing of the Quorum in the Context of <b><i>Pseudomonas aeruginosa</i></b> Infections

“…The LPS provides an effective permeability barrier against antibiotics and antimicrobial peptides. The last-resort antibiotic colistin, also known as polymyxin E, binds to LPS with high affinity; LPS modifications lead to the development of antibiotic resistance and changes in bacterial fitness and virulence potential [39]. LPS is able to enhance bacterial cell surface hydrophobicity, and therefore increase P. aeruginosa motility and impact adhesion and biofilm formation [40].…”