Inactivation of ppk differentially affects virulence and disrupts ATP homeostasis in Salmonella enterica serovars Typhimurium and Gallinarum

McMeechan, Alisdair; Lovell, M. A.; Cogan, Tristan A; Marston, Kerrie L.; Humphrey, Tom J.; Barrow, Paul

doi:10.1016/j.resmic.2006.10.008

Cited by 16 publications

(23 citation statements)

References 32 publications

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“…Similarly, polyphosphate is important for the virulence of bacterial pathogens. In particular, polyphosphate is involved in survival during starvation (e.g., in low phosphate) for Campylobacter jejuni and Salmonella enterica (72,73). The polyphosphate kinase in bacteria is also essential for biofilm formation in Pseudomonas aeruginosa, Vibrio cholerae, and Escherichia coli (74)(75)(76), while deletion of the kinase gene in Campylobacter jejuni increased biofilm formation (72).…”

Section: Discussionmentioning

confidence: 99%

“…The polyphosphate kinase in bacteria is also essential for biofilm formation in Pseudomonas aeruginosa, Vibrio cholerae, and Escherichia coli (74)(75)(76), while deletion of the kinase gene in Campylobacter jejuni increased biofilm formation (72). Virulence during macrophage interaction or during infection of the host was also reduced for polyphosphate metabolism mutants of P. aeruginosa, Helicobacter pylori, C. jejuni, Salmonella enterica, Mycobacterium tuberculosis, and E. coli (72)(73)(74)(76)(77)(78)(79)(80)(81)(82)(83).…”

Section: Discussionmentioning

confidence: 99%

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Defects in Phosphate Acquisition and Storage Influence Virulence of Cryptococcus neoformans

et al. 2014

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Nutrient acquisition and sensing are critical aspects of microbial pathogenesis. Previous transcriptional profiling indicated that the fungal pathogen Cryptococcus neoformans, which causes meningoencephalitis in immunocompromised individuals, encounters phosphate limitation during proliferation in phagocytic cells. We therefore tested the hypothesis that phosphate acquisition and polyphosphate metabolism are important for cryptococcal virulence. Deletion of the high-affinity uptake system interfered with growth on low-phosphate medium, perturbed the formation of virulence factors (capsule and melanin), reduced survival in macrophages, and attenuated virulence in a mouse model of cryptococcosis. Additionally, analysis of nutrient sensing functions for C. neoformans revealed regulatory connections between phosphate acquisition and storage and the iron regulator Cir1, cyclic AMP (cAMP)-dependent protein kinase A (PKA), and the calcium-calmodulin-activated protein phosphatase calcineurin. Deletion of the VTC4 gene encoding a polyphosphate polymerase blocked the ability of C. neoformans to produce polyphosphate. The vtc4 mutant behaved like the wild-type strain in interactions with macrophages and in the mouse infection model. However, the fungal load in the lungs was significantly increased in mice infected with vtc4 deletion mutants. In addition, the mutant was impaired in the ability to trigger blood coagulation in vitro, a trait associated with polyphosphate. Overall, this study reveals that phosphate uptake in C. neoformans is critical for virulence and that its regulation is integrated with key signaling pathways for nutrient sensing.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Defects in Phosphate Acquisition and Storage Influence Virulence of Cryptococcus neoformans

et al. 2014

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“…2B). A number of enteric pathogens lacking ppk1 are also less tolerant to osmotic stress than the parental wild-type strains; these include E. coli, Salmonella spp., and V. cholerae (36,49,59). Although poly-P has been hypothesized to participate in osmotic shock protection by virtue of its polyanion structure (59), specific molecular mechanisms have not yet been elucidated.…”

Section: Figmentioning

confidence: 99%

“…and P. aeruginosa, and for colonization of certain strains of H. pylori (7,49,63,70). Chickens are a natural zoonotic reservoir for C. jejuni, and contamination of commercial broiler flocks is thought to account for the majority of human C. jejuni infections (47).…”

Section: Figmentioning

confidence: 99%

Polyphosphate Kinase 1 Is a Pathogenesis Determinant in Campylobacter jejuni

Allan²,

et al. 2007

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Campylobacter jejuni is the leading cause of bacterial gastroenteritis in the developed world. Despite its prevalence, relatively little is known about C. jejuni's precise pathogenesis mechanisms, particularly in comparison to other well-studied enteric organisms such as Escherichia coli and Salmonella spp. Altered expression of phosphate genes in a C. jejuni stringent response mutant, together with known correlations between the stringent response, polyphosphate (poly-P), and virulence in other bacteria, led us to investigate the role of poly-P in C. jejuni stress survival and pathogenesis. All sequenced C. jejuni strains harbor a conserved putative polyphosphate kinase 1 predicted to be principally responsible for poly-P synthesis. We generated a targeted ppk1 deletion mutant (⌬ppk1) in C. jejuni strain 81-176 and found that ⌬ppk1, as well as the ⌬spoT stringent response mutant, exhibited low levels of poly-P at all growth stages. In contrast, wild-type C. jejuni poly-P levels increased significantly as the bacteria transitioned from log to stationary phase. Phenotypic analyses revealed that the ⌬ppk1 mutant was defective for survival during osmotic shock and low-nutrient stress. However, certain phenotypes associated with ppk1 deletion in other bacteria (i.e., motility and oxidative stress) were unaffected in the C. jejuni ⌬ppk1 mutant, which also displayed an unexpected increase in biofilm formation. The C. jejuni ⌬ppk1 mutant was also defective for the virulence-associated phenotype of intraepithelial cell survival in a tissue culture infection model and exhibited a striking, dose-dependent chick colonization defect. These results indicate that poly-P utilization and accumulation contribute significantly to C. jejuni pathogenesis and affect its ability to adapt to specific stresses and stringencies. Furthermore, our study demonstrates that poly-P likely plays both similar and unique roles in C. jejuni compared to its roles in other bacteria and that poly-P metabolism is linked to stringent response mechanisms in C. jejuni.

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“…살모넬라 생균백신 후보주로는 온도감수성(temperaturesensitive; ts), polyphosphate kinase(ppk), aromatic amino acid(aroA), DNA adenine methylase(dam) 변이주 등이 있 다 [9,14,20]. 이 중 polyphosphate kinase(ppk) 유전자는 세포의 ATP 생성과정에서 polyphosphate(polyP)의 합성에 관여하는 것으로 알려져 있으며 [22], ST ppk 변이주가 야 생주에 비해 쥐 및 닭에서 병원성이 매우 감소되는 것은 이 미 보고된 바 있다 [20]. 또한 온도감수성 변이주는 숙주의 체내에서 증식하지 못하기 때문에 생균백신 후보주로 적합 할 것으로 사료된다.…”

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Development and evaluation of protective capacity of Salmonella Enteritidis polyphosphate kinase-deleted and temperature-sensitive mutant

Kim¹,

Park²,

Cho³

et al. 2013

Korean Journal of Veterinary Science

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: This study was focusing on evaluating the protection of polyphosphate kinase (ppk) deleted and/or temperature-sensitive (ts) Salmonella Enteritidis (SE) as an attenuated vaccine in chickens. We constructed SEppk, SEts and SEppk::ts mutants and screened those mutants by growth capability in vitro, protection study in mice model and antibody response in chickens. Among the mutants, SEppk::ts-3 was selected because it showed higher growth capability, good protection against highly virulent SE in mice model, and good antibody response in chickens. SEppk::ts-3 also showed good protection against highly virulent SE isolate because it decreased colonization of virulent SE challenge strain in spleen, liver and cecum compared with the non-vaccinated control. The SEppk::ts-3 mutant showed crossprotection against S. Gallinarum (SG) challenge although the its cross-protection rate was a little lower than that of SG9R, a commercial vaccine against SG infection. To use for live attenuated vaccine in chickens, it should further be characterized. Keywords

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Inactivation of ppk differentially affects virulence and disrupts ATP homeostasis in Salmonella enterica serovars Typhimurium and Gallinarum

Cited by 16 publications

References 32 publications

Defects in Phosphate Acquisition and Storage Influence Virulence of Cryptococcus neoformans

Defects in Phosphate Acquisition and Storage Influence Virulence of Cryptococcus neoformans

Polyphosphate Kinase 1 Is a Pathogenesis Determinant in Campylobacter jejuni

Development and evaluation of protective capacity of Salmonella Enteritidis polyphosphate kinase-deleted and temperature-sensitive mutant

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