Sheltering Effect and Indirect Pathogenesis of Carbapenem-Resistant Acinetobacter baumannii in Polymicrobial Infection

Abstract

The role of carbapenem-resistant Acinetobacter baumannii (CRAb) in polymicrobial infection remains elusive. Having observed the ability of CRAb to shelter other susceptible bacteria from carbapenem killing, we sought to determine the factors contributing to this sheltering effect by transforming different recombinant plasmids into recipient A. baumannii cells. The sheltering effects of CRAb were reproduced in recipient A. baumannii cells that highly expressed carbapenem-hydrolyzing class D ␤-lactamases (CHDLs) through their associated strong promoter. With the use of Western blot analysis and a bioassay, the highly expressed CHDLs were found to be extracellularly released and led to hydrolysis of carbapenem. The level of extracellular CHDLs increased after challenge with a higher concentration of CHDL substrates, such as carbapenem and ticarcillin. This increased CHDL may, in part, be attributed to cell lysis, as indicated by the presence of extracellular gyrase. In the planktonic condition, the sheltering effect for the cocultured susceptible bacteria might represent an indirect and passive effect of the CRAb self-defense mechanism, because coculture with the susceptible pathogen did not augment the amount of the extracellular CHDLs. Polymicrobial infection caused by CRAb and a susceptible counterpart exerted higher pathogenicity than monomicrobial infection caused by either pathogen alone in mice receiving carbapenem therapy. This study demonstrated that CHDL-producing CRAb appears to provide a sheltering effect for carbapenem-susceptible pathogens via the extracellular release of CHDLs and, by this mechanism, can enhance the pathogenesis of polymicrobial infection in the presence of carbapenem therapy.

Biofilm Models of Polymicrobial Infection

“…An acute pneumonia mouse model was used to evaluate in vivo competition between S. aureus and P. aeruginosa and showed that a P. aeruginosa wild-type strain outcompeted S. aureus, as calculated by the competition index, or the ratio of P. aeruginosa to S. aureus [110]. In a similar murine lung infection model, intratracheally co-inoculated carbapenem-resistant A. baumannii (CRAb) demonstrated synergy by protecting susceptible organisms, such as E. coli, against treatment with antibiotics [28].…”

“…In biofilms and biofilm-related infections, these 'effects' include increased growth, antimicrobial tolerance, virulence and persistence, and enhanced production of exopolysaccharide (EPS) [17][18][19][20][21][22][23][24][25][26][27][28]. Another classic cooperative interaction is metabolic cross-feeding, or syntrophy, where one species makes a metabolic byproduct which enhances the growth of a neighbor [29].…”

Interspecies Dissemination of a Mobilizable Plasmid Harboring bla IMP-19 and the Possibility of Horizontal Gene Transfer in a Single Patient

“…Liao et al reported that extracellular CHDL produced by Acinetobacter baumannii helped other susceptible bacteria to survive against the eradication of carbapenem and named this phenomenon the sheltering effect (31). This effect is strongly affected by a strong promoter of the CHDL gene.…”

Molecular Characterization of Carbapenem Resistant Acinetobacter baumannii in Cancer Patients

“…This indicate a greater importance for the presence of CRAB in clinical settings and emphasize the urgent need for more effective controls of CRAB in polymicrobial infection (Liao et al, 2014). …”