TY - JOUR
T1 - Substantial contribution of SmeDEF, SmeVWX, SmQnr, and heat shock response to fluoroquinolone resistance in clinical isolates of stenotrophomonas maltophilia
AU - Wu, Chao Jung
AU - Lu, Hsu Feng
AU - Lin, Yi Tsung
AU - Zhang, Man San
AU - Li, Li Hua
AU - Yang, Tsuey Ching
N1 - Funding Information:
If a bacterium is in a situation of de-repression of heat shock response, it has a viability superiority at high temperature. The high-temperature cell viability of the wild-type KJ and its derived mutants was assessed. Since KJ grew poorly at 42◦C (data not shown), we tested the bacterial viability of the cells at 40◦C. Compared to that of KJΔRseA, the viability at 40◦C of KJΔRpoEΔRseA was severely compromised, indicating that RpoE is the key sigma factor for heat shock response. This is supported by similar results comparing the viabilities of KJ and KJΔRpoE at 40◦C (Figure 1B). Nevertheless, KJ(pRpoH) did not display better viability at 40◦C than KJ(pRK415) (Figure 1B).
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PY - 2019
Y1 - 2019
N2 - Stenotrophomonas maltophilia is an emerging multi-drug resistant opportunistic pathogen. Although fluoroquinolones (FQ) are still clinically valuable for the treatment of S. maltophilia infection, an increasing prevalence in FQ resistance has been reported. Overexpression of SmeDEF, SmeVWX, and SmQnr, and de-repressed expression of heat shock response are reported mechanisms responsible for FQ resistance in S. maltophilia; nevertheless, some of these mechanisms are identified from laboratory-constructed mutants, and it remains unclear whether they occur in clinical setting. In this study, we aimed to assess whether these mechanisms contribute substantially to FQ resistance in clinical isolates. Eighteen ciprofloxacin- and levofloxacin-resistant isolates were selected from 125 clinical isolates of S. maltophilia. The expression of smeE, smeW, and Smqnr genes of these isolates was investigated by RT-qPCR. The de-repressed heat shock response was assessed by rpoE expression at 37°C and bacterial viability at 40°C. The contribution of SmeDEF, SmeVWX, and SmQnr, and heat shock response to FQ resistance was evaluated by mutants construction and susceptibility testing. The results demonstrated that simply assessing the overexpression of SmeDEF, SmeVWX, and SmQnr by RT-qPCR may overestimate their contribution to FQ resistance. Simultaneous overexpression of SmeDEF and SmeVWX did not increase the resistance level to their common substrates, but extended the resistance spectrum. Moreover, the de-repressed expression of heat shock response was not observed to contribute to FQ resistance in the clinical isolates of S. maltophilia.
AB - Stenotrophomonas maltophilia is an emerging multi-drug resistant opportunistic pathogen. Although fluoroquinolones (FQ) are still clinically valuable for the treatment of S. maltophilia infection, an increasing prevalence in FQ resistance has been reported. Overexpression of SmeDEF, SmeVWX, and SmQnr, and de-repressed expression of heat shock response are reported mechanisms responsible for FQ resistance in S. maltophilia; nevertheless, some of these mechanisms are identified from laboratory-constructed mutants, and it remains unclear whether they occur in clinical setting. In this study, we aimed to assess whether these mechanisms contribute substantially to FQ resistance in clinical isolates. Eighteen ciprofloxacin- and levofloxacin-resistant isolates were selected from 125 clinical isolates of S. maltophilia. The expression of smeE, smeW, and Smqnr genes of these isolates was investigated by RT-qPCR. The de-repressed heat shock response was assessed by rpoE expression at 37°C and bacterial viability at 40°C. The contribution of SmeDEF, SmeVWX, and SmQnr, and heat shock response to FQ resistance was evaluated by mutants construction and susceptibility testing. The results demonstrated that simply assessing the overexpression of SmeDEF, SmeVWX, and SmQnr by RT-qPCR may overestimate their contribution to FQ resistance. Simultaneous overexpression of SmeDEF and SmeVWX did not increase the resistance level to their common substrates, but extended the resistance spectrum. Moreover, the de-repressed expression of heat shock response was not observed to contribute to FQ resistance in the clinical isolates of S. maltophilia.
KW - Efflux pump, Qnr protein
KW - Fluoroquinolone resistance
KW - Heat shock response
KW - Stenotrophomonas maltophilia
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U2 - 10.3389/fmicb.2019.00822
DO - 10.3389/fmicb.2019.00822
M3 - Article
AN - SCOPUS:85068173096
SN - 1664-302X
VL - 10
JO - Frontiers in Microbiology
JF - Frontiers in Microbiology
IS - APR
M1 - 822
ER -