Group B Streptococcus and diabetes: Finding the sweet spot

Keogh, Rebecca A.; Doran, Kelly S.

doi:10.1371/journal.ppat.1011133

Cited by 8 publications

(5 citation statements)

References 37 publications

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“…Furthermore, a state of systemic low-grade inflammation associated with T2DM may exacerbate the inflammatory cascade that accompanies the onset and progression of such infections. Experimental models also suggest that the diabetic milieu promotes GBS survival, eliciting a greater inflammatory response compared to non-diabetic patients [ 10 ] .…”

Section: Discussionmentioning

confidence: 99%

Group B Streptococcus meningitis in an adult woman with type 2 diabetes and ethmoid roof defect. Impact on “frontal” cognitive functions

Vicinanza,

Miscetti,

Magistrato

et al. 2024

European Journal of Case Reports in Internal Medicine

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Background: Community-acquired bacterial meningitis in adults represents one of the most severe infectious diseases worldwide with potentially life-threatening medical complications. Several infectious agents can cause acute meningitis. Although group B Streptococcus is more prevalent in newborns, infection can also lead to meningitis in older adults, particularly those with underlying health issues. Case Description: A 53-year-old woman with a body mass index of 28.7 kg/m2, type 2 diabetes mellitus, and dyslipidaemia presented to the emergency department of Santa Maria della Stella Hospital (Orvieto, Italy) with confusion, low-grade fever, echolalia, and hyperglycaemia. Computed tomography scans of the brain revealed a hypodensity in the left anterior frontal lobe and an osteodural defect of the rhinobase. Meningitis was suspected and empiric broad-spectrum antibiotic therapy with corticosteroids and insulin were administered while the results of the cerebrospinal fluid analysis confirmed the diagnosis of group B Streptococcus meningitis. Repeat imaging at 48 hours revealed enlargement of the hypodense lesion. The frontal assessment battery indicated deficits in executive functions. Prompt treatment led to rapid clinical improvement. Following the restoration of euglycemic status and hemodynamic stabilization, a follow-up magnetic resonance imaging confirmed the ischaemic lesion and showed cerebrospinal fluid in the sella turcica. The patient was then transferred to neurorehabilitation. Conclusions: The complex interactions among multiple risk factors resulted in an atypical clinical case of group B Streptococcus meningitis, which was promptly treated with empiric antibiotic therapy to mitigate neurocognitive deficits.

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Section: Discussionmentioning

confidence: 99%

Group B Streptococcus meningitis in an adult woman with type 2 diabetes and ethmoid roof defect. Impact on “frontal” cognitive functions

Vicinanza,

Miscetti,

Magistrato

et al. 2024

European Journal of Case Reports in Internal Medicine

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“…Mice were wounded with a 6-mm biopsy punch and infected with GBS strains A909 (serotype Ia) or CJB111 (serotype V) ( 2 ). These strains represent the two most common serotypes to cause invasive disease in non-pregnant adults and are commonly isolated from diabetic wounds ( 2 - 5 ). Diabetic (Db) mice lost more weight, had larger wounds, and had increased bacterial burden in wound tissue regardless of GBS strain compared to non-diabetic (nDb) mice ( Fig.…”

Section: Observationmentioning

confidence: 99%

The impact of nutritional immunity on Group B streptococcal pathogenesis during wound infection

Akbari

Keogh

Radin

et al. 2023

mBio

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Group B Streptococcus (GBS) is a Gram-positive pathobiont that can cause adverse health outcomes in neonates and vulnerable adult populations. GBS is one of the most frequently isolated bacteria from diabetic (Db) wound infections but is rarely found in the non-diabetic (nDb) wound environment. Previously, RNA sequencing of wound tissue from Db wound infections in lepr d b diabetic mice showed increased expression of neutrophil factors, and genes involved in GBS metal transport such as the zinc (Zn), manganese (Mn), and putative nickel (Ni) import systems. Here, we develop a Streptozotocin-induced diabetic wound model to evaluate the pathogenesis of two invasive strains of GBS, serotypes Ia and V. We observe an increase in metal chelators such as calprotectin (CP) and lipocalin-2 during diabetic wound infections compared to nDb. We find that CP limits GBS survival in wounds of non-diabetic mice but does not impact survival in diabetic wounds. Additionally, we utilize GBS metal transporter mutants and determine that the Zn, Mn, and putative Ni transporters in GBS are dispensable in diabetic wound infection but contributed to bacterial persistence in non-diabetic animals. Collectively, these data suggest that in non-diabetic mice, functional nutritional immunity mediated by CP is effective at mitigating GBS infection, whereas in diabetic mice, the presence of CP is not sufficient to control GBS wound persistence. IMPORTANCE Diabetic wound infections are difficult to treat and often become chronic due to an impaired immune response as well as the presence of bacterial species that establish persistent infections. Group B Streptococcus (GBS) is one of the most frequently isolated bacterial species in diabetic wound infections and, as a result, is one of the leading causes of death from skin and subcutaneous infection. However, GBS is notoriously absent in non-diabetic wounds, and little is known about why this species thrives in diabetic infection. The work herein investigates how alterations in diabetic host immunity may contribute to GBS success during diabetic wound infection.

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“…Streptococcus agalactiae or group B streptococcus (GBS) is a frequent colonizer of the human intestine that can also cause a wide range of diseases, including sepsis, meningitis, endocarditis, soft tissue infections and arthritis. Infections affecting adults, including patients with chronic underlying disease (such as diabetes and solid tumors) and the elderly, are steadily increasing (Farley, 2001 ; Sambola et al, 2002 ; Zi et al, 2022 ; Keogh and Doran, 2023 ). Moreover, in the neonate, GBS is a highly prevalent cause of serious disease including sepsis, meningoencephalitis, and permanent neurological disorders (Edwards and Baker, 2005 ; Verani et al, 2010 ).…”

Section: Introductionmentioning

confidence: 99%

Engagement of α3β1 and α2β1 integrins by hypervirulent Streptococcus agalactiae in invasion of polarized enterocytes

De Gaetano,

Lentini,

Coppolino

et al. 2024

Front. Microbiol.

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The gut represents an important site of colonization of the commensal bacterium Streptococcus agalactiae (group B Streptococcus or GBS), which can also behave as a deadly pathogen in neonates and adults. Invasion of the intestinal epithelial barrier is likely a crucial step in the pathogenesis of neonatal infections caused by GBS belonging to clonal complex 17 (CC17). We have previously shown that the prototypical CC17 BM110 strain invades polarized enterocyte-like cells through their lateral surfaces using an endocytic pathway. By analyzing the cellular distribution of putative GBS receptors in human enterocyte-like Caco-2 cells, we find here that the alpha 3 (α3) and alpha 2 (α2) integrin subunits are selectively expressed on lateral enterocyte surfaces at equatorial and parabasal levels along the vertical axis of polarized cells, in an area corresponding to GBS entry sites. The α3β1 and α2β1 integrins were not readily accessible in fully differentiated Caco-2 monolayers but could be exposed to specific antibodies after weakening of intercellular junctions in calcium-free media. Under these conditions, anti-α3β1 and anti-α2β1 antibodies significantly reduced GBS adhesion to and invasion of enterocytes. After endocytosis, α3β1 and α2β1 integrins localized to areas of actin remodeling around GBS containing vacuoles. Taken together, these data indicate that GBS can invade enterocytes by binding to α3β1 and α2β1 integrins on the lateral membrane of polarized enterocytes, resulting in cytoskeletal remodeling and bacterial internalization. Blocking integrins might represent a viable strategy to prevent GBS invasion of gut epithelial tissues.

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Group B Streptococcus and diabetes: Finding the sweet spot

Cited by 8 publications

References 37 publications

Group B Streptococcus meningitis in an adult woman with type 2 diabetes and ethmoid roof defect. Impact on “frontal” cognitive functions

Group B Streptococcus meningitis in an adult woman with type 2 diabetes and ethmoid roof defect. Impact on “frontal” cognitive functions

The impact of nutritional immunity on Group B streptococcal pathogenesis during wound infection

Engagement of α3β1 and α2β1 integrins by hypervirulent Streptococcus agalactiae in invasion of polarized enterocytes

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