Expression of the MtsA lipoprotein of Streptococcus agalactiae A909 is regulated by manganese and iron

Bray, Beverley A.; Sutcliffe, Iain C.; Harrington, Dean J.

doi:10.1007/s10482-008-9291-6

Cited by 28 publications

(29 citation statements)

References 51 publications

(79 reference statements)

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“…A good candidate may be the MtsA manganese transporter, whose encoding gene is present in the S. agalactiae genome and which has been shown to bind zinc with low affinity in S. pneumoniae (51,52).…”

Section: Discussionmentioning

confidence: 99%

The Adc/Lmb System Mediates Zinc Acquisition in Streptococcus agalactiae and Contributes to Bacterial Growth and Survival

et al. 2016

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The Lmb protein of Streptococcus agalactiae is described as an adhesin that binds laminin, a component of the human extracellular matrix. In this study, we revealed a new role for this protein in zinc uptake. We also identified two Lmb homologs, AdcA and AdcAII, redundant binding proteins that combine with the AdcCB translocon to form a zinc-ABC transporter. Expression of this transporter is controlled by the zinc concentration in the medium through the zinc-dependent regulator AdcR. Triple deletion of lmb, adcA, and adcAII, or that of the adcCB genes, impaired growth and cell separation in a zinc-restricted environment. Moreover, we found that this Adc zinc-ABC transporter promotes S. agalactiae growth and survival in some human biological fluids, suggesting that it contributes to the infection process. These results indicated that zinc has biologically vital functions in S. agalactiae and that, under the conditions tested, the Adc/Lmb transporter constitutes the main zinc acquisition system of the bacterium. IMPORTANCEA zinc transporter, composed of three redundant binding proteins (Lmb, AdcA, and AdcAII), was characterized in Streptococcus agalactiae. This system was shown to be essential for bacterial growth and morphology in zinc-restricted environments, including human biological fluids. S treptococcus agalactiae (group B streptococcus [GBS]) is aGram-positive commensal bacterium of the human gastrointestinal and uro-genital tracts. GBS carriage is mostly asymptomatic in healthy adults, and this bacterium is detected in the vagina of approximatively 30% of pregnant women. Maternal carriage is the main source of transmission to neonates, in which S. agalactiae can cause invasive infections (pneumonia, septicemia, and meningitis), with an overall mortality rate of approximately 10% (1, 2). GBS is also an emergent pathogen among the elderly and in adults with underlying diseases (1, 3).The ability of GBS to colonize different niches and cause infection is multifactorial, and many virulence-associated proteins have been identified (4, 5). Binding of GBS adhesins to components of the extracellular matrix constitutes a crucial first step in the process of infection (6-9). Among them, the Lmb protein has been identified as a GBS receptor for laminin, a glycosylated multidomain protein found in all human tissues (10). The gene encoding Lmb is located on a transposon with the scpB and sht genes, which encode a C5a peptidase and a histidine triad protein, respectively (11, 12). The lmb promoter region is a hot spot for the integration of two mobile genetic elements. One of them is associated with increased expression of lmb, resulting in increased binding of strains harboring the transposon to laminin (13). It has also been shown that Lmb may promote bacterial invasion in human brain microvascular endothelial cell lines (14).Lmb is clustered by sequence homology as a metal-binding receptor. Indeed, Lmb has strong homology with the zinc-binding proteins AdcA and Lbp of other streptococcal species (15, 16). Th...

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Section: Discussionmentioning

confidence: 99%

The Adc/Lmb System Mediates Zinc Acquisition in Streptococcus agalactiae and Contributes to Bacterial Growth and Survival

et al. 2016

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“…The expression of scavenger proteins, especially those involved in metal acquisition, is often tightly regulated (10,20,28). The reduced transcription of TroA in porcine serum supplemented with manganese and the upregulation of TroA transcripts in vivo (53) strongly suggest the presence of a manganese-dependent TroA transcriptional regulatory mechanism.…”

Section: Discussionmentioning

confidence: 99%

“…To test the virulence of the ⌬troA mutant bacteria in systemic infection, we used a murine infection model broadly used to assess virulence of S. suis mutants (4,9,50). Ten CD1 mice were inoculated intraperitoneally with 10 9 CFU of wild-type or ⌬troA mutant bacteria. Five control mice were injected with D-PBS.…”

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confidence: 99%

TroA of Streptococcus suis Is Required for Manganese Acquisition and Full Virulence

et al. 2011

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Streptococcus suis causes infections in pigs and occasionally in humans, resulting in manifestations as meningitis, sepsis, arthritis, and septic shock. For survival within the host, S. suis requires numerous nutrients including trace metals. Little is known about the specific proteins involved in metal scavenging in S. suis. In this study we evaluated the role of the putative high-affinity metal binding lipoprotein TroA in metal acquisition and virulence. A mutant strain deficient in the expression of TroA (⌬troA mutant) was constructed. Growth of the ⌬troA mutant in Todd-Hewitt broth was similar to wild-type growth; however, growth of the ⌬troA mutant in cation-deprived Todd-Hewitt broth and in porcine serum was strongly reduced compared to growth of wild-type bacteria. Supplementing the medium with extra manganese but not with magnesium, zinc, copper, nickel, or iron restored growth to wild-type levels, indicating that TroA is specifically required for growth in environments low in manganese. The ⌬troA mutant also showed increased susceptibility to H 2 O 2 , suggesting that TroA is involved in counteracting oxidative stress. Furthermore, the expression of the troA gene was subject to environmental regulation at the transcript level. In a murine S. suis infection model, the ⌬troA mutant displayed a nonvirulent phenotype. These data indicate that S. suis TroA is involved in manganese acquisition and is required for full virulence in mice.Streptococcus suis is an important pathogen of pigs and may cause meningitis, sepsis, arthritis, and septic shock. Occasionally, S. suis is able to infect humans. Infected humans may show symptoms similar to those in pigs (1,5,11,32). Although human infections are exceptional, a large outbreak in humans was reported in 2005 in China, with 215 cases and 39 deaths (52). Of the 33 known S. suis serotypes, serotype 2 is most frequently isolated from diseased pigs and humans. However, serotype 9 infections are emerging in pigs, especially in Europe (7,35,48). Current control measures are insufficient and mainly rely on antibiotic treatment and vaccination with homologous bacterins. Increased antibiotic resistance has been reported for S. suis (17, 49), and bacterin-based vaccines do not provide protection against multiple serotypes (6).For growth and function, bacteria have to acquire numerous nutrients from their surrounding environment. For pathogenic bacteria, an important group of essential nutrients are the trace metals. Metals such as iron, zinc, and manganese have been shown to be essential structural and catalytic cofactors for several bacterial proteins (2). However, the concentration of free available trace metals within an infected host is relatively low compared to the metal concentrations in medium usually applied for in vitro growth. Within the host, several trace metals are sequestered; for instance, iron binds to hemoglobin, and zinc and manganese bind to the S100 family of proteins produced by neutrophils (14,15). This recruitment of trace metals by host proteins ha...

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“…S. agalactiae A909 and its derivatives were cultured aerobically in Todd-Hewitt Broth (THB; Oxoid) or anaerobically on Granada medium (Biomedics) at 37 uC. For some experiments, media with depleted metal ion content were prepared by incubating THB with Chelex-100 resin as described previously (Bray et al, 2009). Antibiotics were added to growth media as appropriate to allow selection of antibiotic-resistant GBS strains.…”

Section: Methodsmentioning

confidence: 99%

“…MtsA (SAK_1556) is an experimentally verified Lpp in GBS (Bray et al, 2009;Henneke et al, 2008). Cellular fractions were prepared from strains A909 and A909DLgt and analysed by Western blotting with a polyclonal antibody that cross-reacts with MtsA (Bray et al, 2009). In the parent strain a single cross-reacting band of~34 kDa was seen in all cellular fractions (Fig.…”

Section: Effect Of Lgt Inactivation On Lipoprotein Processingmentioning

confidence: 99%

Impact of lgt mutation on lipoprotein biosynthesis and in vitro phenotypes of Streptococcus agalactiae

2009

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Although Streptococcus agalactiae, the group B Streptococcus, is a leading cause of invasive neonatal disease worldwide the molecular basis of its virulence is still poorly understood. To investigate the role of lipoproteins in the physiology and interaction of this pathogen with host cells, we generated a mutant S. agalactiae strain (A909DLgt) deficient in the Lgt enzyme and thus unable to lipidate lipoprotein precursors (pro-lipoproteins). The loss of pro-lipoprotein lipidation did not affect the viability of S. agalactiae or its growth in several different media, including cationdepleted media. The processing of two well-characterized lipoproteins, but not a non-lipoprotein, was clearly shown to be aberrant in A909DLgt. The mutant strain was shown to be more sensitive to oxidative stress in vitro although the molecular basis of this increased sensitivity was not apparent. The inactivation of Lgt also resulted in changes to the bacterial cell envelope, as demonstrated by reduced retention of both the group B carbohydrate and the polysaccharide capsule and a statistically significant reduction (P50.0079) in A909DLgt adherence to human endothelial cells of fetal origin. These data confirm that failure to process lipoproteins correctly has pleiotropic effects that may be of significance to S. agalactiae colonization and pathogenesis.

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Expression of the MtsA lipoprotein of Streptococcus agalactiae A909 is regulated by manganese and iron

Cited by 28 publications

References 51 publications

The Adc/Lmb System Mediates Zinc Acquisition in Streptococcus agalactiae and Contributes to Bacterial Growth and Survival

The Adc/Lmb System Mediates Zinc Acquisition in Streptococcus agalactiae and Contributes to Bacterial Growth and Survival

TroA of Streptococcus suis Is Required for Manganese Acquisition and Full Virulence

Impact of lgt mutation on lipoprotein biosynthesis and in vitro phenotypes of Streptococcus agalactiae

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