Relationship between colonizer and colonized strep

What is infection vs. colonization?Baylor Scott & White Health

Part of the success of streptococci as colonizers is attributable to the spectrum of Taxonomic relationship tree for Streptococcus based on 16S rRNA gene. The burden from group B streptococcal (GBS) disease in elderly persons (age, ⩾ 65 The GBS colonization rate among healthy elderly participants (mean age, .. to affirm the dominance of type V GBS as a colonizer in elderly subjects. .. B Streptococcus in pregnant Canadian women: relationship to colonization. a patient with colonization but no infection may require isolation if the organism is the relationship between Group A Streptococcus invasive disease and.

The GBS colonization rate among healthy elderly participants mean age, 73 years was CPS types Ia Random selection of 1 member of 33 participating married couples did not alter the overall colonization rate The past 2 decades have witnessed a 2—4-fold increase in the incidence of invasive group B streptococcal GBS disease among nonpregnant adults.

Invasive disease usually occurs in adults with underlying medical conditions or advanced age [ 1 ]. The success of maternal intrapartum antimicrobial prophylaxis has shifted the disease burden from young infants to nonpregnant adults. Inthe case-fatality rate from invasive GBS infection among elderly persons was substantial GBS CPS—specific IgG in maternal serum specimens obtained at the time of delivery has a well-defined role in protecting neonates and young infants from invasive disease, and the concept that colonization precedes the development of invasive infection is well understood [ 8—10 ].

Candidate GBS CPS—protein conjugate vaccines under development offer potential for prevention of perinatal disease and also for disease in nonpregnant adults, including elderly persons [ 11—13 ].

Methods Participants, setting, and procedures. The letter was sent to persons who had previously participated in a study of a vaccine against shingles and had indicated willingness to be notified of future studies of potential interest to them.

Each potential volunteer was interviewed by telephone or in person to ascertain eligibility. Potential subjects were excluded if they had a chronic medical condition known to enhance risk for invasive GBS disease. Exclusion criteria were diagnoses of diabetes mellitus, chronic liver or kidney disease, active malignancy, immunodeficiency, or immunosuppression. Those who met inclusion criteria and were willing to volunteer came to Baylor College of Medicine for an outpatient visit.

After eligibility and current medications were documented, written informed consent was obtained. A small cohort of 40 of these subjects has been described in a previously published report [ 14 ] of the ability of neutrophils and endogenous, CPS-specific IgG to ingest and kill type V GBS.

Specimen collection and laboratory methods. After instruction from study personnel, male volunteers self-obtained a rectal swab specimen and initial void urine specimen. Female subjects self-obtained rectal and lower vaginal swab specimens [ 15 ]. GBS isolates were serotyped by the capillary precipitin method [ 17 ]. The similarity of GBS isolates that were not serologically typeable was determined by visual comparison of PFGE bands for these isolates with those for control strains.

Strains were considered to be identical on the basis of criteria adapted from Tenover et al. Paoletti and Dennis L. Kasper, Channing Laboratory, Boston as the coating antigen. Values that were below the lower limit of detection for the ELISA were assigned a concentration that was one-half that of the lower limit. Data were analyzed with the statistical package SPSS, version SEs were calculated for all mean data results. The Wilcoxon signed rank test was used to compare different CPS-specific antibody and isotype concentrations in serum specimens for all subjects, and the Mann-Whitney U test was used to compare these factors according to sex, age, or colonization status [ 25 ].

Random selection of 1 member of each married couple was accomplished by evaluation of sequential dates of study enrollment and alternate selection of the husband or wife for inclusion. Of the adults interviewed, 30 did not participate 16 did not meet inclusion criteria, and 14 either declined to participate or did not keep a scheduled appointment and were enrolled men [ The mean age was The subjects had been prescribed a mean of 2.

The rate of colonization was nearly identical for men and women. Two-thirds of women were colonized at both vaginal and rectal sites. Strains that were nontypeable constituted CPS types Ib 3. In cases in which both body sites were colonized, the GBS types were concordant in 19 ST-1 invasive isolates from adults and neonates are mostly belonging to serotype V Salloum et al.

The authors regard the emergence of ST-1 strains as a leading cause of adult disease in the s. Similar to human ST, the human ST-1 is suspected to originate from a bovine ancestor. Whole-genome sequencing recognized a ST-1 clone to be closely related to a s Swedish strain causing cow mastitis. The ST-1 human GBS were found to possess mutations at loci involved in capsule production, pilus expression, and two-component regulatory systems Flores et al.

Particular interest should also be paid to the increasing emergence of type IV among colonizing and invasive GBS isolates. In several recent investigations, this serotype appears to be a hotspot for genetic recombination events, supported by the detection of serotype IV strains with different genetic backgrounds.

Multiple studies demonstrated ST as the most frequent sequence type of serotype IV isolates Gherardi et al. However, other investigations reported the STs andbelonging to CCs 23 and 1, respectively, as the predominant colonizing type IV strains and found ST less frequently Diedrick et al.

Comparing a collection of emerging type IV isolates in United States belonging to two distinct time periods from to and from tothe older strains were more like a s prototype reference strain with similar PFGE profiles whereas the more recent isolates showed PFGE profiles with considerable differences Diedrick et al.

Imperialism; Colonizers vs. Colonized

Independent studies identified the invasive characteristics of type IV strains to be a result of capsular switching in CC17 strains accompanied with the acquisition of the HvgA adhesin, which has initially been isolated from hypervirulent CC17 serotype III strains Teatero et al. Capsular switching events of CC17 strains have previously been observed Da Cunha et al.

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Unusual associations are most likely to be due to capsular switching which resulted from recombination events around the capsular locus Teatero et al. Investigation of the increase of type IV strains suggested the evolution of hybrid genomes including sequences from hypervirulent ST strains Teatero et al.

Thus growing evidence points to an ongoing emergence of novel virulent GBS clones requiring continuous epidemiological surveillance. Biofilm Formation Colonization and persistence in different host niches is dependent on the adherence capacity of GBS to host cells and tissues.

This then facilitates bacterial cell aggregation and formation of sessile communities known as biofilms. In the host environment, bacteria are often protected from the immune system by building sessile colonies embedded in an extracellular matrix of polysaccharides representing the biofilm.

For GBS the bacterial capsule and type IIa pili have been demonstrated to play an important role in biofilm formation Konto-Ghiorghi et al. Host environmental conditions are crucial determinants in developing bacterial biofilms Costerton et al.

Contradictory data are available concerning the environmental cues favoring biofilm communities in GBS Rosini and Margarit, As a normal inhabitant of the vagina, acidic pH seems to be optimal for GBS colonization. Early investigations reported enhanced GBS adherence to vaginal epithelial cells under low pH in comparison to neutral pH Zawaneh et al.

In line with these observations, a significantly higher biofilm production of colonizing GBS isolates from pregnant women was demonstrated at pH 4.

Similarly, enhanced biofilm formation of GBS was shown under acidic pH conditions in comparison to neutral pH with the strongest biofilm producing GBS isolates belonged to the ST sequence type.

However, a recent investigation reported invasive GBS belonging to CC17 and CC19 lineages as weak biofilm formers while GBS isolated from asymptomatic carriers were found to be strong biofilm producers Parker et al. One possible explanation for this discrepancy is the experimental set up of the study since GBS biofilm formation was tested at neutral pH conditions and not under acidic pH.

Furthermore, the presence of human plasma was shown to promote GBS biofilm formation Xia et al. In summary, biofilms allow long-term bacterial persistence and protect bacteria from recognition by the immune system. For GBS low pH and the presence of plasma appear as crucial environmental factors through controlling the expression of bacterial surface-associated structures, such as pili and the capsule, which are both involved in promoting bacterial biofilm formation. In addition, surface-protruding structures comprised of multiples genes like pili are considered as essential adhesins in promoting GBS colonization, persistence, biofilm production, and central nervous system invasion.

Major adhesins mediating GBS interaction with host cells are depicted in Figure 1. Major adhesins mediating Streptococcus agalactiae GBS interaction with host cells. GBS colonization, persistence, translocation, and invasion of host barriers are largely dependent on their ability to adhere to host cells and extracellular matrix proteins ECMan important step in breaching cellular barriers.

In addition, surface-protruding structures like pili are considered as essential adhesins in promoting GBS colonization, persistence, biofilm production, and central nervous system invasion. Associated virulence traits are illustrated for each adhesin as follows.

FbsA was mainly shown to promote adherence whereas FbsB was shown to be required for invading human cells. Srr1 and Srr2 were reported to mediate invasion of microvascular endothelial cells.

Additionally, Srr1 was demonstrated to promote vaginal colonization and persistence. FbsC was recently characterized to promote invasion of epithelial and endothelial barriers and biofilm formation.

The Lmb adhesin appears to have a pronounced role in bacterial tropism of the central nervous system CNS. ScpB interrupts complement activation through cleaving the neutrophil chemoattractant C5a. It is also involved in invasion of human epithelial cells.

What is infection vs. colonization?

The SfbA adhesin is involved in human brain microvascular endothelial cells invasion. Furthermore, SfbA contributes to GBS invasion of vaginal and cervical epithelial cells and hence may take part in GBS colonization and niche establishment in the vagina. BibA was reported to aid GBS survival in human blood through interfering with the classic complement pathway by binding the C4-binding protein and by conferring anti-phagocytic activity against opsonophagocytic killing by human neutrophils.

HvgA is specific for the hypervirulent clone ST It was suggested to promote meningeal tropism in neonates. Pili in GBS have been shown to be primarily involved in epithelial cell colonization, biofilm formation, translocation, and invasion.

PI-1 pili were also found to play an important role in evasion of innate immunity mechanism. The PI-2b protein, however, was demonstrated to increase the intracellular survival in macrophage.

Pilus 2b was further identified as important for infection and penetration of the blood brain barrier. In general, invasive GBS isolates display stronger fibrinogen-binding abilities in comparison to colonizing ones Rosenau et al. FbsA was mainly shown to promote adherence Schubert et al. Srr1 and Srr2 were reported to mediate invasion of microvascular endothelial cells Seo et al.

Additionally, Srr1 was demonstrated to promote vaginal colonization and persistence, since a Srr1-deficient mutant displayed reduced persistence in a mouse GBS vaginal colonization model Sheen et al.

FbsC was recently characterized to promote invasion of epithelial and endothelial barriers.

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FbsC deletion mutant of GBS displayed a drastic reduction in abilities for adherence, invasion and biofilm formation. Besides, virulence abilities of FbsC deletion mutant were impaired in murine infection models Buscetta et al. Interestingly, the fibrinogen-binding abilities of the hypervirulent CC17 clones are mainly attributable to FbsB more than FbsA.

Accordingly, the relative transcription level of fbsB was up to Moreover, Srr2 was highly expressed and exclusively detected in ST, however, Srr1 was absent Seifert et al. Furthermore, CC17 strains are devoid of FbsC. The fbsC gene is not adequately expressed in CC17 strains because of a lineage-dependent frameshift mutation Buscetta et al.

In addition to the Fbs family, the Lmb adhesin appears to have a pronounced role in bacterial tropism of the central nervous system. This role was later confirmed by Tenenbaum et al. In consistence, Al Safadi et al. ScpB or the group B ScpB is a surface associated serine protease that both interrupts complement activation through splitting the neutrophil chemoattractant C5a and mediates bacterial binding to fibronectin Chmouryguina et al.

The fibronectin binding ability conferred by the scpB gene appears to be involved in cellular adherence and invasion. In frame deletion mutation of scpB gene significantly reduced invasion of human epithelial cells in vitro Cheng et al. Strikingly, scpB and lmb genes were found to be encoded on a composite transposon where the scpB gene is positioned directly upstream of the lmb gene. The scpB-lmb intergenic region has been described as a hot spot for integration of the GBS mobile genetic elements GBSil and IS which are located in the promoter region of the lmb gene Franken et al.

Al Safadi et al. However, no influence was observed on the scpB gene. Deletion mutation of IS revealed IS to act as an lmb gene up-regulator when compared to the wild-type parent strains. Interestingly the ability of GBS to colonize human mucosal surfaces seems to be closely linked to the presence of this composite transposon carrying scpB and lmb. More recently, a novel GBS fibronectin binding protein has been identified Mu et al.

It was designated as streptococcal fibronectin-binding protein A SfbA and reported to be highly conserved in GBS mediating cellular invasion but not adherence. SfbA was shown to be directly involved in fibronectin binding and human brain microvascular endothelial cells invasion. When expressed in recombinant non-pathogenic Lactococcus lactis, fibronectin binding ability was significantly greater in comparison to a SfbA negative control strain.

The investigation also demonstrated SfbA to be primarily involved in brain microvascular endothelial cells invasion. Infection of mice with sfbA mutants resulted in a reduced ability to breach the blood brain barrier and subsequent meningitis. This is supported by a study showing SfbA to be crucial for invasion of astrocytes which are physically associated with the brain endothelial cells Stoner et al.

Furthermore, SfbA contributes to GBS invasion of vaginal and cervical epithelial cells and hence may take part in GBS colonization and niche establishment in the vagina Mu et al. Another fibronectin binding protein was described in Jiang and Wessels, BsaB or the bacterial surface adhesin of GBS is a fibronectin and laminin-binding protein which is involved in GBS binding to epithelial cells and in biofilm formation.

Deletion of bsaB gene and a cotranscribed upstream region significantly abrogated GBS adherence to VK2 vaginal epithelial cells in vitro and immobilized fibronectin. However, genome and sequence analysis revealed BsaB and FbsC as identical proteins encoded by the same gene Buscetta et al.

Hence, BsaB was renamed to FbsC. The multitude of GBS adhesins allowing attachment to different ECM, stresses the importance of this step in GBS pathogenesis, which was confirmed in different in vivo models.

In this regard, fibrinogen binding may play an especially important role as demonstrated by the presence of numerous fibrinogen binding proteins. It is a cell wall-anchored protein which is well-conserved in GBS and is involved in bacterial binding to human epithelial cells Santi et al.

A knockout mutant displayed impaired adherence capacity to the lung, intestinal, and cervical epithelial cells Santi et al. Overexpression of BibA resulted in increased adherence to human epithelial cells in recombinant wild-type strains harboring a bibA plasmid Santi et al. In addition, BibA was reported to aid GBS survival in human blood through interfering with the classic complement pathway by binding the C4-binding protein and by conferring anti-phagocytic activity against opsonophagocytic killing by human neutrophils Santi et al.

Interestingly, variant IV, which was found to be highly similar to the bovine BibA counterparts, was exclusively associated with ST strains Lamy et al. It contributes to GBS mucosal colonization and adherence to host cells and then confers resistance to phagocytic killing at a stage when the switch to invasive GBS infection has occurred. It was first described Tazi et al. It was suggested to promote meningeal tropism in neonates through efficient intestinal colonization and subsequent translocation across the intestinal and the blood brain barriers.

Bypassing intestinal colonization by intravenous infection resulted in a significant decrease in the amount of bacteria reaching the central nervous system. HvgA was required for intestinal colonization in orally infected mice for meningitis development.

In addition, HvgA was found to mediate GBS adherence to intestinal epithelial cells, choroid epithelial cells, and microvascular endothelial cells Tazi et al. Clones expressing HvgA exhibited greater adherence abilities than non-expressing ones.

HvgA thus contributes to colonization as well as invasion of hypervirulent clones Tazi et al. Different from their Gram-negative counterparts, pili in GBS have been shown to be primarily involved in epithelial cell colonization, biofilm formation, translocation, and invasion.

Pili are cell-wall anchored appendages extending from the bacterial surface. They contain covalently linked multimeric motifs that are composed of three pilin proteins, the pilus shaft backbone protein BP or PilB subunits, and the two ancillary proteins AP1, AP2 located at the pilus tip PilA subunit, the pilus-associated adhesin and pilus base PilC subunit, the pilus anchorrespectively, Dramsi et al.

While PilB has been shown to be involved in bacterial invasion and paracellular translocation mediating resistance to phagocytic killing and virulence, PilA was found contributing to cellular adherence and colonization Dramsi et al. All characterized GBS strains harbored at least one variant or a combination of two pilus islands Rosini et al.

Strikingly, PI-1 pili do not appear to contribute to bacterial adhesion to lung, vaginal or cervical epithelial cells Jiang et al. The PI-2b protein, however, was demonstrated to increase the intracellular survival in macrophage Chattopadhyay et al. In addition, a special role for pilus type 2b has been suggested in promoting strain invasiveness and bacterial host cell interactions.