Acquisition of factor H by a novel surface protein on group B<i>Streptococcus</i>promotes complement degradation

Maruvada, Ravi; Prasadarao, Nemani V.; Rubens, Craig E.

doi:10.1096/fj.09-138149

Cited by 30 publications

(27 citation statements)

References 50 publications

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“…lmb is located on a 16-kb composite transposon containing the scpB, lmb, and sht genes (11,12). We performed BLASTN searches on available genomic DNA sequences of S. agalactiae (n ϭ 271) and identified the presence of the lmb-containing transposon in 96.8% of the 187 human isolates and only 26.7% of the 84 animal isolates (mainly fish and cattle), in agreement with previous observations for 30 human and 38 bovine strains (11).…”

Section: Resultssupporting

confidence: 87%

“…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.…”

Section: S Treptococcus Agalactiae (Group B Streptococcus [Gbs]) Is Amentioning

confidence: 99%

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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: Resultssupporting

confidence: 87%

Section: S Treptococcus Agalactiae (Group B Streptococcus [Gbs]) Is Amentioning

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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“…To date most of the work describing the interactions between S. agalactiae and complement components has primarily focused on the role of sialic acid-rich capsule (6) and factor H-binding proteins (12,29) in the prevention of C3-mediated opsonization through inhibition of the AP. Low levels of maternal anti-capsular polysaccharide IgG correlate with an increased neonatal susceptibility to GBS infection (30), and a higher amount of these Abs increases the efficiency of GBS killing by polymorphonuclear phagocytes via a complement-dependent mechanism involving the AP (31,32).…”

Section: Discussionmentioning

confidence: 99%

“…These include the b protein, which interacts with the factor H complement regulator (10) and sialic acid-binding Siglec-5 lectin expressed on leukocyte surfaces (11), the histidine triad protein STH, which also binds factor H promoting complement degradation (12), and BibA, a group B Streptococcus immunogenic bacterial adhesin that specifically binds to human C4b-binding protein (13).…”

Section: S Treptococcus Agalactiae (Group B Streptococcus [Gbs])mentioning

confidence: 99%

The Group B Streptococcus–Secreted Protein CIP Interacts with C4, Preventing C3b Deposition via the Lectin and Classical Complement Pathways

Pietrocola

Rindi

Rosini³

et al. 2016

The Journal of Immunology

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The group B Streptococcus (GBS) is a leading cause of neonatal invasive disease. GBS bacteria are surrounded by a thick capsular polysaccharide that is a potent inhibitor of complement deposition via the alternative pathway. Several of its surface molecules can however activate the classical and lectin complement pathways, rendering this species still vulnerable to phagocytic killing. In this study we have identified a novel secreted protein named complement interfering protein (CIP) that downregulates complement activation via the classical and lectin pathways, but not the alternative pathway. The CIP protein showed high affinity toward C4b and inhibited its interaction with C2, presumably preventing the formation of the C4bC2a convertase. Addition of recombinant CIP to GBS cip-negative bacteria resulted in decreased deposition of C3b on their surface and in diminished phagocytic killing in a whole-blood assay. Our data reveal a novel strategy exploited by GBS to counteract innate immunity and could be valuable for the development of anti-infective agents against this important pathogen.

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“…Among their putative roles, neutralization of the complement factor C3b through factor H binding has been suggested (Hostetter, 1999;Ogunniyi et al, 2009), which implies that they would interfere with phagocytosis. This assumption is further sustained by the fact that the group B Streptococcus Pht homologue (named streptococcal histidine triad) seems also to bind factor H (Maruvada et al, 2009). However, other authors, through the use of Pht-deficient strains, concluded that these proteins do not bind factor H (Melin et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Transcriptional regulation, occurrence and putative role of the Pht family of Streptococcus pneumoniae

Rioux¹,

Neyt²,

Paolo³

et al. 2011

Microbiology

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Restricted to the genus Streptococcus, the Pht protein family comprises four members: PhtA, PhtB, PhtD and PhtE. This family has the potential to provide a protein candidate for incorporation in pneumococcal vaccines. Based on sequence analysis and on RT-PCR experiments, we show here that the pht genes are organized in tandem but that their expression, except that of phtD, is monocistronic. PhtD, PhtE, PhtB and PhtA are present in 100, 97, 81 and 62 % of the strains, respectively, and, by analysing its sequence conservation across 107 pneumococcal strains, we showed that PhtD displays very little variability. To analyse the physiological function of these proteins, several mutants were constructed. The quadruple Pht-deficient mutant was not able to grow in a poor culture medium, but the addition of Zn 2+ or Mn 2+ restored its growth capacity.Moreover, the phtD mRNA expression level increased when the culture medium was depleted in zinc. Therefore, we suggest that these proteins are zinc and manganese scavengers, and are able to store these metals and to release them when the bacterium faces an ion-restricted environment. The data also showed that this protein family, and more particularly PhtD, is a promising candidate to be incorporated into pneumococcal vaccines.

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Acquisition of factor H by a novel surface protein on group BStreptococcuspromotes complement degradation

Cited by 30 publications

References 50 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

The Group B Streptococcus–Secreted Protein CIP Interacts with C4, Preventing C3b Deposition via the Lectin and Classical Complement Pathways

Transcriptional regulation, occurrence and putative role of the Pht family of Streptococcus pneumoniae

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