Recognition of mechanisms involved in bile resistance important to halting antimicrobial resistance in nontyphoidal Salmonella

Tsai, Ming Han; Wu, Sih Ru; Lee, Hao Yuan; Chen, Chyi Liang; Lin, Tzou Yien; Huang, Yhu Chering; Chiu, Cheng Hsun

doi:10.1016/j.ijantimicag.2012.04.016

Cited by 10 publications

(9 citation statements)

References 27 publications

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“…In view of the antibacterial mechanism of PB and constitutive expression of S . maltophilia SmeZ [ 7 ], increased PB susceptibility in smeZ mutant should be due to the membrane disturbance [ 38 ]. As expected, S .…”

Section: Discussionmentioning

confidence: 99%

Stenotrophomonas maltophilia PhoP, a Two-Component Response Regulator, Involved in Antimicrobial Susceptibilities

Liu¹,

Tsai²,

Huang³

et al. 2016

PLoS ONE

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Stenotrophomonas maltophilia, a gram-negative bacterium, has increasingly emerged as an important nosocomial pathogen. It is well-known for resistance to a variety of antimicrobial agents including cationic antimicrobial polypeptides (CAPs). Resistance to polymyxin B, a kind of CAPs, is known to be controlled by the two-component system PhoPQ. To unravel the role of PhoPQ in polymyxin B resistance of S. maltophilia, a phoP mutant was constructed. We found MICs of polymyxin B, chloramphenicol, ampicillin, gentamicin, kanamycin, streptomycin and spectinomycin decreased 2–64 fold in the phoP mutant. Complementation of the phoP mutant by the wild-type phoP gene restored all of the MICs to the wild type levels. Expression of PhoP was shown to be autoregulated and responsive to Mg2+ levels. The polymyxin B and gentamicin killing tests indicated that pretreatment of low Mg2+ can protect the wild-type S. maltophilia from killing but not phoP mutant. Interestingly, we found phoP mutant had a decrease in expression of SmeZ, an efflux transporter protein for aminoglycosides in S. maltophilia. Moreover, phoP mutant showed increased permeability in the cell membrane relative to the wild-type. In summary, we demonstrated the two-component regulator PhoP of S. maltophilia is involved in antimicrobial susceptibilities and low Mg2+ serves as a signal for triggering the pathway. Both the alteration in membrane permeability and downregulation of SmeZ efflux transporter in the phoP mutant contributed to the increased drug susceptibilities of S. maltophilia, in particular for aminoglycosides. This is the first report to describe the role of the Mg2+-sensing PhoP signaling pathway of S. maltophilia in regulation of the SmeZ efflux transporter and in antimicrobial susceptibilities. This study suggests PhoPQ TCS may serve as a target for development of antimicrobial agents against multidrug-resistant S. maltophilia.

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Section: Discussionmentioning

confidence: 99%

Stenotrophomonas maltophilia PhoP, a Two-Component Response Regulator, Involved in Antimicrobial Susceptibilities

Liu¹,

Tsai²,

Huang³

et al. 2016

PLoS ONE

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“…Conventional antibiotics, such as ampicillin, chloramphenicol, and trimethoprim/sulfamethoxazole, are no longer an appropriate choice for the treatment of invasive salmonellosis 21. Increasing antimicrobial resistance in NTS is a global public health problem that complicates antimicrobial therapy, and is increasingly due to the overuse and misuse of antimicrobial agents in animal feeds 22–24. Several studies worldwide have reported increased morbidity and mortality in patients infected with resistant Salmonella strains 25,26.…”

Section: Discussionmentioning

confidence: 99%

Prevalence of nontyphoidal Salmonella serogroups and their antimicrobial resistance patterns in a university teaching hospital in Eastern Province of Saudi Arabia

Elhadi¹,

Aljindan²,

Aljeldah³

2013

IDR

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BackgroundNontyphoidal Salmonella (NTS) species are important food-borne pathogens that cause gastroenteritis and bacteremia, and are responsible for a huge global burden of morbidity and mortality. The aim of this study was to investigate the prevalent serogroups and antibiotic resistance of NTS in our region.MethodsWe reviewed the serogroup distribution and antimicrobial susceptibility patterns of NTS strains obtained from 158 stool specimens of patients with acute diarrheal infection attending the outpatient and inpatient department at a university hospital in the Eastern Province of Saudi Arabia in the period from September, 2008 to April, 2011. A retrospective analysis of the 158 patients with NTS infection was conducted to determine the most prevalent NTS serogroups causing acute gastroenteritis and their antimicrobial susceptibility patterns.ResultsAt this teaching hospital, a total of 17,436 fecal samples were analyzed during the 2008–2011 study period. Of these specimens, 158 tested positive for NTS, giving an overall prevalence of 9.06 per 1,000. Of 158 NTS cases, serogroup D1 (25.3%) was the most prevalent, followed by serogroup B (19.6%), and serogroup C1 (18.9). One third of all NTS serogroup strains tested were resistant to tetracycline. The NTS strains showed resistance to ampicillin (31.3%), amoxicillin/clavulanic acid (29.9%), trimethoprim/sulfamethoxazole (20.9%), and cefotaxime (14.93%).ConclusionThe findings of this study support the concern that use of antibiotics in animal feeds may contribute to acquisition of resistance in food-borne bacteria, such as Salmonella. Our study also concludes that the prevalence of NTS in the Eastern Province of Saudi Arabia is very low compared with other studies worldwide.

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“…The resulting pool of bile acid variants is stored in the gallbladder, until hormone release during digestion prompts the release of bile into the duodenum. High bile acid concentrations (up to 2%) are maintained in the duodenum, jejunum, and proximal ileum (21,22). In the ileum and colon, 95% of bile acids are recovered by the host and returned to the liver.…”

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confidence: 99%

Bile Acids Function Synergistically To Repress Invasion Gene Expression in Salmonella by Destabilizing the Invasion Regulator HilD

et al. 2016

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bSalmonella spp. are carried by and can acutely infect agricultural animals and humans. After ingestion, salmonellae traverse the upper digestive tract and initiate tissue invasion of the distal ileum, a virulence process carried out by the type III secretion system encoded within Salmonella pathogenicity island 1 (SPI-1). Salmonellae coordinate SPI-1 expression with anatomical location via environmental cues, one of which is bile, a complex digestive fluid that causes potent repression of SPI-1 genes. The individual components of bile responsible for SPI-1 repression have not been previously characterized, nor have the bacterial signaling processes that modulate their effects been determined. Here, we characterize the mechanism by which bile represses SPI-1 expression. Individual bile acids exhibit repressive activity on SPI-1-regulated genes that requires neither passive diffusion nor OmpF-mediated entry. By using genetic methods, the effects of bile and bile acids were shown to require the invasion gene transcriptional activator hilD and to function independently of known upstream signaling pathways. Protein analysis techniques showed that SPI-1 repression by bile acids is mediated by posttranslational destabilization of HilD. Finally, we found that bile acids function synergistically to achieve the overall repressive activity of bile. These studies demonstrate a common mechanism by which diverse environmental cues (e.g., certain short-chain fatty acids and bile acids) inhibit SPI-1 expression. These data provide information relevant to Salmonella pathogenesis during acute infection in the intestine and during chronic infection of the gallbladder and inform the basis for development of therapeutics to inhibit invasion as a means of repressing Salmonella pathogenicity.

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Recognition of mechanisms involved in bile resistance important to halting antimicrobial resistance in nontyphoidal Salmonella

Cited by 10 publications

References 27 publications

Stenotrophomonas maltophilia PhoP, a Two-Component Response Regulator, Involved in Antimicrobial Susceptibilities

Stenotrophomonas maltophilia PhoP, a Two-Component Response Regulator, Involved in Antimicrobial Susceptibilities

Prevalence of nontyphoidal Salmonella serogroups and their antimicrobial resistance patterns in a university teaching hospital in Eastern Province of Saudi Arabia

Bile Acids Function Synergistically To Repress Invasion Gene Expression in Salmonella by Destabilizing the Invasion Regulator HilD

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