The manganese efflux system MntE contributes to the virulence of Streptococcus suis serotype 2

Xu, Jiali; Zheng, Chengkun; Cao, Man; Zhang, Ting; Zhao, Xigong; Shi, Guolin; Chen, Huanchun; Bei, Weicheng

doi:10.1016/j.micpath.2017.06.022

Cited by 22 publications

(33 citation statements)

References 28 publications

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“…The increased availability of intracellular Mn could enhance Mn-dependent antioxidant defenses, as has been reported in Streptococcus spp . (10, 12). Alternatively, increased intracellular Mn could lead to increase sensitivity to oxidative stress as reported for Xanthomonas oryzae and S. pyogenes (8, 12, 39).…”

Section: Resultsmentioning

confidence: 99%

“…(10, 12). Alternatively, increased intracellular Mn could lead to increase sensitivity to oxidative stress as reported for Xanthomonas oryzae and S. pyogenes (8, 12, 39). However, the E. faecalis mntE∷Tn mutant did not display altered sensitivity to oxidizing agents when compared to wild type (Figure S6A-B) , nor did hydrogen peroxide production significantly change when compared to wild type, as has been reported for S. pneumoniae when Mn is in excess (9) (Figure S6C) .…”

Section: Resultsmentioning

confidence: 99%

“…In Streptococcus pneumoniae and Streptococcus pyogenes , deletion of the mntE results in increased sensitivity to Mn toxicity and intracellular Mn accumulation (9, 10, 24). Similarly, in Streptococcus suis , deletion of mntE results in increased sensitivity to Mn toxicity and, like S. pyogenes , displays increased sensitivity to oxidative stress (10, 12). Additionally, MntE mutants in S. pneumoniae and S. suis are attenuated in mouse models of infection (9, 12).…”

Section: Introductionmentioning

confidence: 99%

“…Similarly, in Streptococcus suis , deletion of mntE results in increased sensitivity to Mn toxicity and, like S. pyogenes , displays increased sensitivity to oxidative stress (10, 12). Additionally, MntE mutants in S. pneumoniae and S. suis are attenuated in mouse models of infection (9, 12). In Staphylococcus aureus , an mntE mutant displays increased sensitivity to Mn and oxidative stress when grown in Mn enriched media, and accumulates intracellular Mn (25).…”

Section: Introductionmentioning

confidence: 99%

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Enterococcus faecalis manganese exporter MntE alleviates manganese toxicity and is required for mouse gastrointestinal colonization

Lam

Wong

Chong

et al. 2020

Preprint

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26Bacterial pathogens encounter a variety of nutritional environments in the human host, 27 including nutrient metal restriction and overload. Uptake of manganese (Mn) is essential for 28 Enterococcus faecalis growth and virulence; however, it is not known how this organism 29 prevents Mn toxicity. In this study, we examine the role of the highly conserved MntE 30 transporter in E. faecalis Mn homeostasis and virulence. We show that inactivation of mntE 31 results in growth restriction in the presence of excess Mn, but not other metals, demonstrating 32 its specific role in Mn detoxification. Upon growth in the presence of excess Mn, an mntE 33 mutant accumulates intracellular Mn, iron (Fe), and magnesium (Mg), supporting a role for 34 MntE in Mn and Fe export, and a role for Mg in offsetting Mn toxicity. Growth of the mntE 35 mutant in excess Fe also results in increased levels of intracellular Fe, but not Mn or Mg, 36 providing further support for MntE in Fe efflux. Inactivation of mntE in the presence of 37 excess iron also results in the upregulation of glycerol catabolic genes and enhanced biofilm 38 growth, and addition of glycerol is sufficient to augment biofilm growth for both the mntE 39 mutant and its wild type parental strain, demonstrating that glycerol availability significantly 40 enhances biofilm formation. Finally, we show that mntE contributes to infection of the 41 antibiotic-treated mouse gastrointestinal (GI) tract, suggesting that E. faecalis encounters 42 excess Mn in this niche. Collectively, these findings demonstrate that the manganese exporter 43 MntE plays a crucial role in E. faecalis metal homeostasis and virulence. 44 45 nutritional immunity (1, 4-6). To counteract these host-mediated defences, many bacterial 51 pathogens including Enterococci encode dedicated systems to acquire Mn. 52 53Bacteria encode conserved ABC and NRAMP-family transporters for manganese uptake (1, 54 2). In Enterococcus faecalis, three manganese uptake systems have been described: the ABC-55 type transporter encoded by efaCBA and two NRAMP transporters encoded by mntH1 and 56 mntH2 (7). These three Mn transport systems are functionally redundant since deletion of all 57 three transporter systems (efaCBA, mntH1, mntH2) is required to abrogate intracellular Mn 58 accumulation, rendering the triple mutant severely impaired in growth (7). Furthermore, 59 deletion of both efaCBA and mntH2, or all three transporters together results in attenuated 60 colonization in rabbit endocarditis and mouse catheter-associated urinary tract infection 61 (CAUTI) models (7). Together these observations demonstrate that the ability to acquire Mn 62 is essential for E. faecalis virulence. 64In contrast to Mn influx mechanisms that have been characterized in E. faecalis, Mn export 65 pathways have not been described. The contribution of Mn export to bacterial pathogenesis 66 and virulence has been demonstrated for some bacterial species (8-15) and is dependent on 67 two widely characterized classes of exporters -MntE, a cat...

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Enterococcus faecalis manganese exporter MntE alleviates manganese toxicity and is required for mouse gastrointestinal colonization

Lam

Wong

Chong

et al. 2020

Preprint

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“…Lai et al [65] identified in the S. suis type 9 strain the presence of a type VII secretion system (T7SS) putative substrate EsxA that contributes to bacterial virulence. Xu et al [66] identified in the S. suis type 2 strain the manganese efflux system MntE which controls the manganese homeostasis that is important for the pathogenesis of this bacterium. Wang at al.…”

Section: Other Virulence Factorsmentioning

confidence: 99%

Streptococcus suis: a re-emerging pathogen associated with occupational exposure to pigs or pork products. Part II – Pathogenesis

Dutkiewicz

Zając

Sroka

et al. 2018

Ann Agric Environ Med.

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Streptococcus suis is a re-emerging zoonotic pathogen that may cause severe disease, mostly meningitis, in pigs and in humans having occupational contact with pigs and pork, such as farmers, slaughterhose workers and butchers. The first stage of the pathogenic process, similar in pigs and humans, is adherence to and colonisation of mucosal and/or epithelial surface(s) of the host. The second stage is invasion into deeper tissue and extracellular translocation of bacterium in the bloodstream, either free in circulation or attached to the surface of monocytes. If S. suis present in blood fails to cause fatal septicaemia, it is able to progress into the third stage comprising penetration into host's organs, mostly by crossing the blood-brain barrier and/or blood-cerebrospinal fluid barrier to gain access to the central nervous system (CNS) and cause meningitis. The fourth stage is inflammation that plays a key role in the pathogen esis of both systemic and CNS infections caused by S. suis. The pathogen may induce the overproduction of pro-inflammatory cytokines that cause septic shock and/or the recruitment and activation of different leukocyte populations, causing acute inflammation of the CNS. Streptococcus suis can also evoke - through activation of microglial cells, astrocytes and possibly other cell types - a fulminant inflammatory reaction of the brain which leads to intracranial complications, including brain oedema, increased intracranial pressure, cerebrovascular insults, and deafness, as a result of cochlear sepsis. In all stages of the pathogenic process, S. suis interacts with many types of immunocompetent host's cells, such as polymorphonuclear leukocytes, mononuclear macrophages, lymphocytes, dendritic cells and microglia, using a range of versatile virulence factors for evasion of the innate and adaptive immune defence of the host, and for overcoming environmental stress. It is estimated that S. suis produces more than 100 different virulence factors that could be classified into 4 groups: surface components or secreted elements, enzymes, transcription factors or regulatory systems and transporter factors or secretion systems. A major virulence factor is capsular polysaccharide (CPS) that protects bacteria from phagocytosis. However, it hampers adhesion to and invasion of host's cells, release of inflammatory cytokines and formation of the resistant biofilm which, in many cases, is vital for the persistence of bacteria. It has been demonstrated that the arising by mutation unencapsulated S. suis clones, which are more successful in penetration to and propagation within the host's cells, may coexist in the organism of a single host together with those that are encapsulated. Both 'complementary' clones assist each other in the successful colonization of host's tissues and persistence therein. S. suis has an open pan-genome characterized by a frequent gene transfer and a large diversity. Of the genetic determinants of S. suis pathogenicity, t...

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Streptococcus suis pathogenesis—A diverse array of virulence factors for a zoonotic lifestyle

Tram

Jennings

Blackall

et al. 2021

Advances in Microbial Physiology

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The manganese efflux system MntE contributes to the virulence of Streptococcus suis serotype 2

Cited by 22 publications

References 28 publications

Enterococcus faecalis manganese exporter MntE alleviates manganese toxicity and is required for mouse gastrointestinal colonization

Enterococcus faecalis manganese exporter MntE alleviates manganese toxicity and is required for mouse gastrointestinal colonization

Streptococcus suis: a re-emerging pathogen associated with occupational exposure to pigs or pork products. Part II – Pathogenesis

Streptococcus suis pathogenesis—A diverse array of virulence factors for a zoonotic lifestyle

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