The inactivation of RNase G reduces the Stenotrophomonas maltophilia susceptibility to quinolones by triggering the heat shock response

Abstract

Quinolone resistance is usually due to mutations in the genes encoding bacterial topoisomerases. However, different reports have shown that neither clinical quinolone resistant isolates nor in vitro obtained Stenotrophomonas maltophilia mutants present mutations in such genes. The mechanisms so far described consist on efflux pumps’ overexpression. Our objective is to get information on novel mechanisms of S. maltophilia quinolone resistance. For this purpose, a transposon-insertion mutant library was obtained in S. maltophilia D457. One mutant presenting reduced susceptibility to nalidixic acid was selected. Inverse PCR showed that the inactivated gene encodes RNase G. Complementation of the mutant with wild-type RNase G allele restored the susceptibility to quinolones. Transcriptomic and real-time RT-PCR analyses showed that several genes encoding heat-shock response proteins were expressed at higher levels in the RNase defective mutant than in the wild-type strain. In agreement with this situation, heat-shock reduces the S. maltophilia susceptibility to quinolone. We can then conclude that the inactivation of the RNase G reduces the susceptibility of S. maltophilia to quinolones, most likely by regulating the expression of heat-shock response genes. Heat-shock induces a transient phenotype of quinolone resistance in S. maltophilia.

Analysis of multidrug resistance in Streptococcus suis ATCC 700794 under tylosin stress

“…A heat shock protein in Stenotrophomonas maltophilia acted as a stress-responsive protein by inducing quinolone resistance [25]. Additionally, a study demonstrates role of the heat shock protein GrpE that has proved early exposure to these drugs in E. coli [53].…”

“…Heat shock proteins are stress-responsive proteins which act as chaperonins to fold proteins. Many heat shock proteins (HSP) such as DnaJ, DnaK, GroEL, GroES, and GrpE have been differentially expressed in drug-resistant strains [25][26][27][28]. They play a role in the development of drug resistance by providing coping mechanism during the early stages of exposure to drugs in E. coli [29].…”

Effect of antibiotics on bacterial populations: a multi-hierarchical selection process

“…The study of the effect of such concentrations has shown that they can have deep effects on bacterial physiology. Indeed, in addition to triggering the expression of shock-response systems 104– 107 , the antibiotics can induce specific bacterial responses. Some of them, dealing with the expression of virulence factors or motility, are specific to each family of drugs 36 ; however, some others seem to be more general.…”

Genome-wide analysis shows that RNase G plays a global role in the stability of mRNAs in Stenotrophomonas maltophilia

“…RNases G from E. coli and S. maltophilia have not significant differences in domains, sequence or length, except for few differences in single amino acids. We have previously shown that the absence of RNase G is associated with increased resistance to quinolones and with the overexpression of genes involved in the S. maltophilia heat shock response 18 , indicating that RNase G might be involved in the cellular response to stress.…”

“…S. maltophilia is an opportunistic pathogen, associated with nosocomial infections, which presents a low level of susceptibility to several antibiotics, including quinolones 19 . The low susceptibility of this pathogen is partly due to the presence in its genome of genes encoding a wide range of resistance determinants 18 , 20 – 28 . Although during the past years much knowledge on the genomic structure complexity of S. maltophilia was obtained, transcriptomic studies and mRNA degradation studies were not performed in this microorganism.…”