The Role of Fluoroquinolones in the Promotion of Alginate Synthesis and Antibiotic Resistance in Pseudomonas aeruginosa

Abstract

Treatment of nonmucoid Pseudomonas aeruginosa with gyrase inhibitors such as ciprofloxacin, norfloxacin, and ofloxacin, which target the A subunit of topoisomerase II, resulted in 100% conversion to the mucoid phenotype. However, antibiotics that partially inhibited growth and macromolecular synthesis (DNA, RNA, protein, or peptidoglycan) of nonmucoid isolates in a gluconate-limited chemostat culture system did not promote conversion to mucoid subpopulations. An increase in resistance was observed in populations that expressed the mucoid phenotype. Both mucoid conversion and antibiotic resistance were completely reversible when ciprofloxacin pressure was withdrawn, but only partially reversible by the removal of norfloxacin and ofloxacin. Thus, these experiments indicate that in the presence of some fluoroquinolones, a conditional response resulting in mucoid conversion and antibiotic resistance may occur.

Bacterial predator-prey coevolution accelerates genome evolution and selects on virulence-associated prey defences

“…In our experiments, mucoidy—a virulence factor in some human pathogens 38 —evolved preferentially and pervasively as a minority phenotype among prey exposed to M. xanthus predation, showing that a generalist bacterial predator drives sympatric phenotype diversification of its prey. Intriguingly, mucoid colony phenotypes have also evolved in response to interaction with lytic phages 39 , macrophages 38 and antibiotics 51 and have been associated with increased survival of protist grazing 52 connecting this phenotypic state to an extremely divergent range of antagonistic interactions. Our finding that multiple prey traits associated with virulence in pathogens (OmpT and mucoidy) were targets of adaptation specifically among coevolved prey suggests that virulence-trait evolution may often be indirectly shaped by selective forces unrelated to pathogenesis 53 .…”

Adaptation to Parasites and Costs of Parasite Resistance in Mutator and Nonmutator Bacteria

“…However, mucoidy can subsequently be repressed by mutations at other sites, hypothesized to result from adaptation to regulate costly expression of this phenotype (Marvig et al 2015 ). More generally, mucoidy can also alter bacterial adaptation to other diverse stresses including antibiotics (Piña and Mattingly 1997 ), macrophages (Miskinyte et al 2013 ), menthol (Landau and Shapira 2012 ), and dessication (Ophir and Gutnick 1994 ). Therefore, we speculate that acquisition of mucoidy and regulation of associated costs, as observed in our experiments, may be common features of bacterial adaptation.…”

The transition metal gallium disrupts Pseudomonas aeruginosa iron metabolism and has antimicrobial and antibiofilm activity

“…The link between Fe and biofilm formation (9)(10)(11)(12) and the fact that Ga can disrupt Fe-dependent processes (21) led us to investigate the effect of Ga on P. aeruginosa biofilm development. Studying Ga's effects on biofilms was also of interest because low concentrations of a number of antibiotics promote biofilm formation, perhaps because biofilm growth can be induced as a consequence of stress (22)(23)(24)(25). These findings have raised the worrisome possibility that antibiotic concentrations that fail to completely kill may actually promote chronic infection.…”