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Background   Stenotrophomonas maltophilia , an opportunistic pathogen, is ubiquitously present in various environments, signifying its high capability of environmental adaptation. Two-component regulatory system (TCS) is a powerful implement to help organisms to survive in different environments. In clinic, treatment of  S. maltophilia  infection is difficult because it is naturally resistant to many antibiotics, highlighting the necessity to develop novel drugs or adjuvants. Given their critical and extensively regulatory role, TCS system has been proposed as a convincing target for novel drugs or adjuvants. PhoPQ TCS, a highly conserved TCS in several pathogens, plays crucial roles in low-magnesium adaption, polymyxin resistance, and virulence. In this study, we aimed to characterize the role of PhoPQ TCS of  S. maltophilia  in antibiotic susceptibility, physiology, stress adaptation, and virulence.    Results  To characterize PhoPQ system,  phoP  single mutant as well as  phoP  and  phoQ  double mutant were constructed. Distinct from most  phoPQ  systems of other microorganisms, two features were observed during the construction of  phoP  and  phoQ  single deletion mutant. Firstly, the  phoQ  mutant was not successfully obtained. Secondly, the compromised phenotypes of  phoP  mutant were not reverted by complementing an intact  phoP  gene, but were partially restored by complementing a  phoPQ  operon. Thus, wild-type KJ,  phoP  mutant (KJΔPhoP) , phoPQ  mutant (KJΔPhoPQ), and complemented strain (KJΔPhoPQ (pPhoPQ)) were used for functional assays, including antibiotic susceptibility, physiology (swimming motility and secreted protease activity), stress adaptation (oxidative, envelope, and iron-depletion stresses), and virulence to  Caenorhabditis elegans . KJΔPhoPQ totally lost swimming motility, had enhanced secreted protease activity, increased susceptibility to antibiotics (β-lactam, quinolone, aminoglycoside, macrolide, chloramphenicol, and sulfamethoxazole/ trimethoprim), menadione, H 2 O 2 , SDS, and 2,2′-dipyridyl, as well as attenuated virulence to  C. elegans . Trans-complementation of KJΔPhoPQ with  phoPQ  reverted these altered phenotypes to the wild-type levels.    Conclusions  Given the critical and global roles of PhoPQ TCS in antibiotic susceptibility, physiology, stress adaptation, and virulence, PhoPQ is a potential target for the design of drugs or adjuvants.

bmc microbiology

PhoPQ two-component regulatory system plays a global regulatory role in antibiotic susceptibility, physiology, stress adaptation, and virulence in Stenotrophomonas maltophilia