TABLE 1.

Summary of synergistic interactions between GBS and other microbes from clinical and experimental studies^a

Host or model	Interaction	Population or condition/intervention	Sample type or medium	Cohort or sample size	Study type	Key finding(s)	Reference
Humans	Bifidobacterim spp.	Newborns of GBS− and GBS+ (and IAP-treated) mothers	Stool	52 newborns	Cross-sectional	IAP-exposed newborns have decreased gastrointestinal bifidobacteria, of which some strains were found to have antibacterial properties against GBS.	51
	Candida albicans	Nonpregnant	Urine and urogenital discharge	>2,400 participants	Cross-sectional	Urogenital GBS was coisolated with enterococci, Staphylococcus saprophyticus, and C. albicans.	193
		Nonpregnant	Not specified	56 participants	Retrospective	GBS was most common bacterial coisolate in a cohort of recurrent vulvovaginal candidiasis patient samples.	194
		Pregnant	Vaginal wash	13,914 participants	Prospective	Candida colonization was accompanied by GBS in 36.8% of samples collected.	195
		Pregnant	Vaginal swab	150 participants	Cross-sectional	Candida spp. were found in 14.9% of GBS+ women compared to 2.9% of GBS− women.	41
		Pregnant	Vaginal swab	623 participants	Cross-sectional	Of the 7% of healthy vaginal samples in which GBS was detected, C. albicans was coisolated in 54.5% of those samples.	42
	Candida spp.	Pregnant	Vaginal swab	7,742 participants	Cross-sectional	Risk of cervicovaginal colonization with GBS was increased with dual GBS and Candida sp. colonization.	196
		Pregnant	Vaginal swab	405 participants	Prospective	Risk of GBS colonization was increased in women cocolonized with Candida.	43
		Pregnant	Rectal and vaginal swab	100 participants	Cross-sectional	GBS prevalence was increased in women cocolonized with Candida.	197
		Pregnant	Vaginal swab	221 participants	Longitudinal	GBS and Candida were coisolated in 26.6% of samples.	198
	Candida spp.	Pregnant	Vaginal swab	542 participants	Cross-sectional	GBS and Candida were coisolated in 36% of GBS+ samples.	132
	Enterococcus spp.
	Staphylococcus aureus
	Candida albicans	Pregnant and nonpregnant	Vaginal swab	430 participants	Cross-sectional	GBS had a higher risk of detection in samples with C. albicans (37.0%) and E. coli (24.6%) than in those without dual colonization. Conversely, E. coli had a higher risk of detection in GBS+ (43.3%) vs GBS− samples.	44
	Escherichia coli
	Escherichia coli	Nonpregnant	Midstream and catheter urine	202 paired samples	Cross-sectional	GBS and E. coli were cocultured from midstream urine and catheter urine collections.	167
		Pregnant	Urine	821 participants	Retrospective	GBS and E. coli were cocultured from uterine cultures taken during nonelective cesarean sections.	163
		Nonpregnant	Endocervical swab	61 participants	Randomized trial	Of participants using a candidate HIV prophylactic, the GBS concn was inversely associated with inhibitory activity against E. coli.	165
	Escherichia coli	Nonpregnant	Rectal and vaginal swab	1,248 participants	Prospective	Rectal GBS colonization is a predictor of GBS vaginal colonization. Other risk factors for GBS vaginal colonization include concurrent vaginal E. coli or yeast colonization.	162
	Yeast
	Escherichia coli	Women diagnosed with vulvovaginitis	Vaginal swab	4 participants	Case study	GBS was coisolated with E. coli and S. aureus.	148
	Staphylococcus aureus
	Escherichia coli	Women diagnosed with tubo-ovarian abscess	Laparotomy drainage	11 participants	Case study	GBS was coisolated with multiple aerobic and anaerobic microbes.	164
	Eubacterium lentum
	Porphyromonas spp.
	Prevotella spp.
	Salmonella sp.
	Staphylococcus spp.
	Streptococcus viridans
	Atopobium vaginae	Pregnant	Vaginal swab	248 participants	Prospective	GBS+ samples correlated with different species depending on thresholds set and analysis via cultivation or WGS.	46
	Bifidobacterium spp.
	Megasphaera sp.
	Prevotella spp.
	Clostridiaceae	Infants of GBS+ mothers	Stool	298 participants	Longitudinal	Once adjusted for demographic parameters and use of IAP, GBS+ status in mothers was associated with variation in gut microbiota composition in samples from the 6-mo visit.	50
	Enterococcaceae
	Ruminococcaceae
	Bacteroidetes	Nonpregnant	Vaginal swab	66 participants	Cross-sectional	After filtering for taxa with a logarithmic discriminant analysis score of ≥3, 10 taxa were positively associated with GBS+ status. Note that Streptococcus as a correlate has been omitted since it was not distinguished from GBS.	33
	Bacteroidia
	Bacteroidales
	Clostridia
	Clostridiales
	Megasphaera
	Prevotella
	Prevotellaceae
	Veillonellaceac
	Prevotella spp.	Diabetic patient	Scrotal abscess	1 participant	Case study	GBS and Prevotella were cocultured.	187
		Pregnant	Vaginal swab	72 participants	Prospective longitudinal	Of the women who received IAP for GBS, Prevotella relative abundance increases postpartum.	185
	Eubacterium siraeum	Nonpregnant	Vaginal lavage specimen	432 participants	Cross-sectional	After filtering for taxa with a logarithmic discriminant analysis score of ≥2.5, 8 taxa were positively associated with GBS+ status.	32
	Finegoldia magna
	Prevotella bivia
	Prevotella melaninogenica
	Peptostreptococcus anaerobiius
	Staphylococcus spp.
	Veillonella spp.
	Staphylococcus aureus	Pregnant	Vaginal swab	4,025 participants	Cross-sectional	GBS+ status was associated with reduced coculture with Gram-positive cocci, anaerobes, and fungi, but also an increased association with specific microbes.	40
	Klebsiella pneumoniae
	Staphylococcus aureus	Nonpregnant	Sterile site culture	19,512 samples	Population-based surveillance	S. aureus was the most common coisolate (46.2%) in GBS polymicrobial sepsis cases.	139
		Nonpregnant	Blood	94 cases	Retrospective	GBS was most commonly coisolated with S. aureus or K. pneumonia.	142
		Patients diagnosed with pneumonia	Blood and respiratory samples	1,791 cases	Retrospective	Of those identified with polymicrobial cultures, 20% were coisolated with S. aureus and 7% with P. aeruginosa	143
		Patients diagnosed with bone or joint infection	Deep surgical sample, joint aspirate, or blood	26 cases	Retrospective	GBS was found more often in polymicrobial than monomicrobial infections. Staphylococcus spp. (S. aureus and S. ludgunesis) and E. faecalis were found in 56% and 19% of samples, respectively.	144
		Men	Skin, urinary or respiratory tract, blood, abscess, joint, bone, or unknown	23 cases	Retrospective	Of patients with bacteremia, GBS was coisolated with B. fragilis, other beta-hemolytic Streptococcus spp., S. aureus, and Providencia stuartii.	140
		Nonpregnant adults and neonates	Blood	18 cases	Retrospective	S. aureus was the most common coisolate in GBS bacteremia.	141
		Infants	Nasopharyngeal swab	1,200 participants	Cross-sectional	Risk of GBS colonization increased with the detection of S. aureus.	137
		Pregnant	Rectal and vaginal swab	2,963 samples	Prospective	S. aureus prevalence was increased in GBS+ samples.	127
		Pregnant women and neonates	Rectal and vaginal swab	2,702 women and 2,789 infants	Retrospective	Risk of S. aureus colonization increased with the detection of GBS.	131
		Pregnant	Rectal and vaginal swab	2,921 samples	Prospective	GBS colonization was positively associated with S. aureus.	130
		Pregnant	Vaginal swab	6,626 participants	Cross-sectional	Risk of S. aureus colonization increased in patients with GBS.	128
		Pregnant	Rectal and vaginal swab	5,732 participants	Prospective	Risk of S. aureus colonization increases with positive GBS colonization status.	129
	Trichomonas vaginalis	Patients with vaginitis	Vaginal swab	327 participants	Cross-sectional	GBS was positively associated with T. vaginalis infection.	35
Cows (Holstein)	Aeromonas spp.	Dairy herds	Milk	7 cows	Cross-sectional	GBS− subclinical mastitis milk was dominant in Firmicutes and was associated with an increase in 2 taxa.	3
	Chryseobacterium spp.
Mice (KK-Ay)	Klebsiella pneumoniae	Laboratory colony	Submandibular abscess and uterine tissue	2 mice	Case study	Of the cultures taken from submandibular abscesses, K. pneumoniae was coisolated. Of the 1 uterine culture, S. aureus was coisolated.	119
	Staphylococcus aureus
Rats	Staphylococcus spp.	Pups from MWF-hDTR laboratory colony	Spleen, kidney, and heart	4 rats	Case study	GBS was cocultured with coagulase-negative Staphylococcus spp. in limb abscesses, and E. coli was coisolated from a liver.	120
	Escherichia col
	Escherichia coli	Female adults from Long-Evans laboratory colony	Spleen, vaginal swab, cervical, nares, lung, brain, uterine, fetal, cardiac thrombus	2 rats	Case study	GBS was coisolated with multiple microbes from different tissue sites or lavage specimens.	121
	Enterobacter aerogenes
	Enterococcus spp.
	Staphylococcus sciuri
	Streptococcus mitis
	Streptococcus oralis
Exptl models	Interaction	Condition/intervention	Sample type or medium	Sample size		Key finding(s)	Reference
In vivo
Mice (CD-1)	Akkermansia municiphila	GBS challenge following pretreatment or cocolonization with A. muciniphila	Vaginal lavage specimen	Not specified		GBS persistence in the vaginal lumen was increased in mice dually colonized with A. muciniphila.	175
Nile tilapia	Akkermansia spp.	Oral gavage with GBS strain YM001	Intestinal tissue	30 fish		Administration of YM001 caused temporary and nonlethal changes in the intestinal gut microbiota, making it a safe vaccine.	106
	Bacteroides spp.
Mice
C57BL/6J	Candida albicans	Transurethral coinfection of C. albicans and GBS	Bladder	14–18 mice/group		C. albicans increased GBS colonization and epithelial adherence through hypha-specific adhesin Als3.	200
		Vaginal coinoculation of C. albicans and GBS	Vaginal lavage specimen	6 mice/group		The vaginal mucosal Th17 response to C. albicans is reduced in the presence of GBS.	199
C3H/HeN and C3H/HeJ	Escherichia coli	Urinary tract coexposure to GBS and UPEC	Bladder	>10 mice/group		Immune response against UPEC is dampened by GBS sialic acid host immune signaling.	168
C57BL/6J	Gardnerella vaginalis	Vaginal coinoculation of GBS and G. vaginalis	Maternal vaginal, uterine, and placental tissues	31 mice		Risk for vaginal colonization, ascension into the uterus, and presence in both the maternal and fetal sides of the placenta increase in the presence of G. vaginalis.	192
Rats (Wistar)	Prevotella bivia	Uterine inoculation with P. bivia and GBS	Uterine fluid	10 rats/group		P. bivia uterine infection is increased by GBS.	186
In vitro	Candida albicans	C. albicans and GBS coculture in vitro	Spider agar and YPD	Triplicate		GBS suppresses hyphal formation through reduction of EFG1/Hwp1 expression.	199
		Cocultivation of C. albicans and GBS	Yeast nitrogen base	Triplicate		GBS BspA protein promoted association of GBS with C. albicans hyphae.	201
		Cocultivation of C. albicans and GBS and cocolonization of vaginal epithelial cells	Keratinocyte serum-free medium	Triplicate		Interaction between GBS and C. albicans increases with hyphal form via C. albicans adhesin Als3 and GBS Bsp adhesins.	202
		Cocultivation of C. albicans and GBS	Blood agar	110 C. albicans strains		C. albicans and GBS demonstrate cohemolytic (CAMP factor like) activity.	203
	Escherichia coli	Cross-feeding assays on solid media and liquid culture	M17 glucose agar	Not specified		E. coli produces ubiquinone, menaquinones, and other metabolites that may be utilized by GBS.	166
	Staphylococcus aureus	Culture of S. aureus with supernatants from bacteria associated with dysbiosis and health	BHI	Not specified		GBS supernatant increased S. aureus tst gene expression encoding toxic shock syndrome protein TSST-1.	145
		Coculture of GBS with bacterial species commonly found in female genital tract	TSB agar	Not specified		S. aureus was not inhibited by GBS isolates.	146

^asp., single unspecified or unknown species of a genus; spp., more than one unspecified or unknown species of a genus; IAP, intrapartum antibiotic prophylaxis; UPEC, uropathogenic E. coli; YPD, yeast extract-peptone-dextrose; BHI, brain heart infusion; TSB, tryptic (or Trypticase) soy broth.