Inhibition of swarming and virulence factor expression in Proteus mirabilis by resveratrol

Abstract

Resveratrol (3,5,4-trihydroxy-trans-stilbene) is a phytoalexin compound with anti-inflammatory and antioxidant activities. The effect of resveratrol on swarming and virulence factor expression of Proteus mirabilis, an important pathogen infecting the urinary tract, was determined on swarming agar plates with and without the compound. Bacteria harvested at different times were assayed for cell length and the production of flagella, haemolysin and urease. Resveratrol inhibited P. mirabilis swarming and virulence factor expression in a dose-dependent manner. Resveratrol significantly inhibited swarming at 15 mg ml , and completely inhibited swarming at 60 mg ml "1 . Inhibition of swarming and virulence factor expression was mediated through RsbA, a His-containing phosphotransmitter of the bacterial two-component signalling system possibly involved in quorum sensing. Complementation of an rsbA-defective mutant with the rsbA gene restored its responsiveness to resveratrol. The compound also inhibited the ability of P. mirabilis to invade human urothelial cells. These findings suggest that resveratrol has potential to be developed as an antimicrobial agent against P. mirabilis infection. INTRODUCTIONProteus mirabilis, a motile Gram-negative enteric bacterium, is an important pathogen of the urinary tract, and is the primary infectious agent in patients with indwelling urinary catheters (Warren et al., 1982). Individuals suffering from urinary tract infections caused by P. mirabilis often develop bacteriuria, cystitis, kidney and bladder stones, catheter obstruction due to stone encrustation, acute pyelonephritis, and fever (Burall et al., 2004;Johnson et al., 1993;Mobley & Warren, 1987).The ability of P. mirabilis to colonize the surfaces of catheters and the urinary tract is believed to be aided by a characteristic known as swarming differentiation and migration (Allison et al., 1994). P. mirabilis swarming involves the coordinate differentiation of short, motile, vegetative cells with a few peritrichous flagella into multinucleate, aseptate swarm cells of up to 40 times the vegetative cell length, and with more than a 50-fold greater surface density of flagella. The swarm cells migrate coordinately and rapidly away from the colony as multicellular rafts until they pause (consolidation) and undergo some de-differentiation (Allison & Hughes, 1991b; Rauprich et al., 1996). Regular cycles of migration and consolidation generate a colony on the agar surface with a characteristic pattern of concentric rings (Allison & Hughes, 1991b; Rauprich et al., 1996). Several potential virulence factors may be responsible for the pathogenicity of P. mirabilis. Among them, flagella, necessary for motility, are involved in establishing infection (Harmon et al., 1989). Urease, which is responsible for the formation of bladder and kidney stones at later stages of infection (Mobley & Hausinger, 1989), can facilitate the colonization of the urinary tract in a mouse model (Jones et al., 1990). Haemolysin, which is cytotoxic for cultured ur...

Effect of Ibicella lutea on uropathogenic Proteus mirabilis growth, virulence, and biofilm formation

“…These results were similar to those reported by Ahuja et al [13] and Labrecque et al [28] who observed that cranberry juice concentrate had neither antibacterial activity on uropathogenic E. coli nor on Porphyromonas gingivalis. The results were also similar to those obtained by Wang et al [31] who suggested that the inhibitory effect of resveratrol, a naturally occurring phytoalexin, on P. mirabilis swarming and virulence factors expression is unlikely to be due to its inhibitory effect on bacterial growth.…”

“…Wang et al [31] evaluated the effect of resveratrol on swarming of P. mirabilis and they observed that this compound also inhibited P. mirabilis swarming in a dose-dependent manner.…”

Impact of cigarette smoke exposure on host-bacterial pathogen interactions

“…Although salmeterol also seems to protect the respiratory epithelium against H. influenzae-induced damage [126], in vivo data show that inhalation of this bronchodilator may negatively influence the effective clearance of NTHi from the murine respiratory tract [127]. In contrast, resveratrol has been shown to ameliorate Serratia marcescens-induced acute pneumonia in rats [128], inhibit swarming and virulence factor expression in Proteus mirabilis [129], be a potential candidate against various Helicobacter pylori-related gastric pathogenic processes [130], and selectively inhibit N. gonorrhoeae and N. meningitidis [131]. in urinary tract infections caused by uropathogenic Escherichia coli [132].…”

Is it Quantum Sentience or Quantum Consciousness? A Review of Social Behaviours Observed in Primitive and Present-Day Microorganisms

“…When the swarm encounters a prey, they kill and lyse the cells using lytic enzymes by a technique called as 'rippling' which helps the bacteria to effectively lyse and absorb the nutrients of the prey (Velicer et al, 2000;Berleman et al, 2008). A similar type of social behaviour is also seen in enteric bacterium Proteus mirabilis, which uses the swarming technique for movement of the colony and for collective preying (Wang et al, 2006b). There are several other behaviours in bacteria that have evolved over time as a means to survive and sense the environment in a solitary as well as collective manner.…”