oxyR , a LysR-Type Regulator Involved in Klebsiella pneumoniae Mucosal and Abiotic Colonization

Abstract

Colonization of the gastrointestinal tract is the first event in Klebsiella pneumoniae nosocomial infections, followed by colonization of the bladder or respiratory tract or entry into the bloodstream. To survive in the host, bacteria must harbor specific traits and overcome multiple stresses. OxyR is a conserved bacterial transcription factor with a key role both in the upregulation of defense mechanisms against oxidative stress and in pathogenesis by enhancing biofilm formation, fimbrial expression, and mucosal colonization. A homolog of oxyR was detected in silico in the K. pneumoniae sequenced genome and amplified from the LM21 wild-type strain. To determine the role of oxyR in K. pneumoniae host-interaction processes, an oxyR isogenic mutant was constructed, and its behavior was assessed. At concentrations lower than 10 7 ml ؊1 , oxyR-deficient organisms were easily killed by micromolar concentrations of H 2 O 2 and exhibited typical aerobic phenotypes. The oxyR mutant was impaired in biofilm formation and types 1 and 3 fimbrial gene expression. In addition, the oxyR mutant was unable to colonize the murine gastrointestinal tract, and in vitro assays showed that it was defective in adhesion to Int-407 and HT-29 intestinal epithelial cells. The behavior of the oxyR mutant was also determined under hostile conditions, reproducing stresses encountered in the gastrointestinal environment: deletion of oxyR resulted in higher sensitivity to bile and acid stresses but not to osmotic stress. These results show the pleiotropic role of oxyR in K. pneumoniae gastrointestinal colonization.

Identification of Gene Products Involved in the Oxidative Stress Response of Moraxella catarrhalis

“…4). A similar phenotype has been reported for oxyR mutants of both P. aeruginosa (10) and Klebsiella pneumoniae (11). The addition of exogenous catalase to the medium allowed the M. catarrhalis oxyR mutant to form single colonies at levels equivalent to those obtained with the wild-type parent strain.…”

“…(60) genome first identified an ORF encoding a protein with similarity to OxyR, a LysR family transcriptional regulator first studied in E. coli (7,51). In both this enteric organism and other Gram-negative bacterial pathogens, OxyR has been shown to be an important regulator of the bacterial response to oxidative stress (9,11,14,24). OxyR is a redox-sensitive transcriptional regulator in E. coli that has two functional domains (28,33).…”

“…In other bacteria, including Neisseria gonorrhoeae (56) and Pseudomonas putida (12), however, OxyR can function as a repressor for some target genes. Mutants lacking the ability to express OxyR are usually more susceptible to killing by H 2 O 2 than are their wild-type parent strains (6,11,27), but there are exceptions to this rule (e.g., N. gonorrhoeae [56]). …”

Unraveling the Mechanism for the Viability Deficiency of Shewanella oneidensis oxyR Null Mutant

“…In bacteria in which OxyR functions solely as an activator, this universal phenotype resulting from the oxyR mutation has been conveniently attributed to the reduced H 2 O 2 -scavenging capacity (20)(21)(22)(23). Our data suggest that this may not be the case, at least in the context of S. oneidensis.…”

“…Conceivably, E. coli cells lacking the oxyR gene are hypersensitive to H 2 O 2 (15,16). While this phenotype is regarded as the hallmark for the oxyR mutants, the impacts of loss of the gene appear to be broad and diverse (17)(18)(19)(20). The oxyR mutants are highly susceptible to redox-cycling agents, such as medadione and paraquat, which induce O 2 Ϫ generation, but not to organic peroxides, such as tert butyl hydroperoxide (21).…”