{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T13:22:17Z","timestamp":1788268937285,"version":"build-2803163510"},"reference-count":38,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Louisiana at Lafayette College of Sciences Dean\u2019s startup funds"},{"id":[{"id":"https:\/\/ror.org\/01x8rc503","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["5R21AI165939-02"],"award-info":[{"award-number":["5R21AI165939-02"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"award":["5R21AI165939-02"],"award-info":[{"award-number":["5R21AI165939-02"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Vernon & Ruby Langlinais research fund in the Ray P. Authement College of Sciences"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Diabetes mellitus (DM) increases the risk of Streptococcus agalactiae (group B Streptococcus; GBS) urinary tract infections (UTIs) and severe complications, including pyelonephritis and bacteremia, although underlying molecular mechanisms are unclear. We hypothesized that DM-associated alterations in urinary tract immunity drive GBS-UTI susceptibility. To address this hypothesis, we examined GBS-UTI pathogenesis in db\/db obese hyperglycemic mice. At 24 h post-infection, diabetic (D-) mice showed significantly higher GBS burden in the bladder and the spleen compared to non-diabetic (ND-) controls. This was accompanied by significant dysregulation of the local innate immune response, including reduced leukocyte recruitment and blunted pro-inflammatory cytokine production in both the bladder and kidneys. We also identified sex differences in GBS tissue tropism. D-females showed a higher bladder burden than ND-females, ND-males, and D-males. In contrast, significantly higher kidney burden in ND-males than ND-females was further exacerbated by DM. This correlated with pronounced differences in CXCL-1 levels between male and female bladders in both D and ND cohorts, although sex did not affect immune cell recruitment. Together, these results suggest an association between obese hyperglycemia-mediated increased susceptibility to GBS-UTI and systemic dissemination and impaired local immune responses. In addition, our results also reveal sex-dependent differences in GBS urinary tract colonization.<\/jats:p>","DOI":"10.3390\/pathogens15090923","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T12:41:18Z","timestamp":1788266478000},"page":"923","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Diabetes Mellitus Affects Urinary Tissue Tropism of Group B Streptococci in a Sex-Dependent Manner"],"prefix":"10.3390","volume":"15","author":[{"given":"Preeti P.","family":"John","sequence":"first","affiliation":[{"name":"School of Biological Sciences, University of Louisiana at Lafayette, Lafayette, LA 70504, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4114-3433","authenticated-orcid":false,"given":"Bidhan","family":"Gautam","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, University of Louisiana at Lafayette, Lafayette, LA 70504, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3911-035X","authenticated-orcid":false,"given":"Kenneth A.","family":"Rogers","sequence":"additional","affiliation":[{"name":"New Iberia Research Center, University of Louisiana at Lafayette, Lafayette, LA 70560, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Ritwij","family":"Kulkarni","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, University of Louisiana at Lafayette, Lafayette, LA 70504, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1038\/nrurol.2010.190","article-title":"The epidemiology of urinary tract infection","volume":"7","author":"Foxman","year":"2010","journal-title":"Nat. Rev. Urol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Kline, K.A., and Lewis, A.L. (2016). Gram-Positive Uropathogens, Polymicrobial Urinary Tract Infection, and the Emerging Microbiota of the Urinary Tract. Microbiol. Spectr., 4.","DOI":"10.1128\/microbiolspec.UTI-0012-2012"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1086\/422321","article-title":"Prevalence of group B streptococcus colonization and potential for transmission by casual contact in healthy young men and women","volume":"39","author":"Manning","year":"2004","journal-title":"Clin. Infect. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1093\/infdis\/jiaa110","article-title":"Burden of Adults Hospitalized with Group B Streptococcal Infection","volume":"224","author":"McLaughlin","year":"2020","journal-title":"J. Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1086\/432804","article-title":"Group B streptococcal infections in elderly adults","volume":"41","author":"Edwards","year":"2005","journal-title":"Clin. Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/1574-6968.12204","article-title":"Asymptomatic bacteriuria: Prevalence rates of causal microorganisms, etiology of infection in different patient populations, and recent advances in molecular detection","volume":"346","author":"Ipe","year":"2013","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"ofy030","DOI":"10.1093\/ofid\/ofy030","article-title":"Obesity, Diabetes, and the Risk of Invasive Group B Streptococcal Disease in Nonpregnant Adults in the United States","volume":"5","author":"Pitts","year":"2018","journal-title":"Open Forum Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"77","DOI":"10.3855\/jidc.10503","article-title":"Argentinian multicenter study on urinary tract infections due to Streptococcus agalactiae in adult patients","volume":"13","author":"Vigliarolo","year":"2019","journal-title":"J. Infect. Dev. Ctries."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1001\/archinte.1997.00440230087011","article-title":"Group B streptococcus bacteremia in nonpregnant adults","volume":"157","author":"Munoz","year":"1997","journal-title":"Arch. Intern. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"386","DOI":"10.3109\/23744235.2015.1131330","article-title":"The changing epidemiology of group B streptococcus bloodstream infection: A multi-national population-based assessment","volume":"48","author":"Ballard","year":"2016","journal-title":"Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1056\/NEJM199306243282503","article-title":"A population-based assessment of invasive disease due to group B Streptococcus in nonpregnant adults","volume":"328","author":"Farley","year":"1993","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2055","DOI":"10.1128\/JCM.00154-09","article-title":"Diversity of group B streptococcus serotypes causing urinary tract infection in adults","volume":"47","author":"Ulett","year":"2009","journal-title":"J. Clin. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1006\/mgme.2001.3185","article-title":"Impairment of type III group B Streptococcus-stimulated superoxide production and opsonophagocytosis by neutrophils in diabetes","volume":"73","author":"Mazade","year":"2001","journal-title":"Mol. Genet. Metab."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S0924-8579(03)00234-6","article-title":"Pathogenesis and management of bacterial urinary tract infections in adult patients with diabetes mellitus","volume":"22","author":"Hoepelman","year":"2003","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/dmrr.682","article-title":"Common infections in diabetes: Pathogenesis, management and relationship to glycaemic control","volume":"23","author":"Peleg","year":"2007","journal-title":"Diabetes Metab. Res. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1093\/infdis\/jiaa443","article-title":"Exposure to Moderate Glycosuria Induces Virulence of Group B Streptococcus","volume":"223","author":"John","year":"2021","journal-title":"J. Infect. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e0000422","DOI":"10.1128\/msphere.00004-22","article-title":"Glycosuria Alters Uropathogenic Escherichia coli Global Gene Expression and Virulence","volume":"7","author":"Islam","year":"2022","journal-title":"mSphere"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e00932-19","DOI":"10.1128\/mSphere.00932-19","article-title":"Host Cathelicidin Exacerbates Group B Streptococcus Urinary Tract Infection","volume":"5","author":"Patras","year":"2020","journal-title":"mSphere"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1007\/s00125-007-0886-7","article-title":"The mechanisms of alloxan- and streptozotocin-induced diabetes","volume":"51","author":"Lenzen","year":"2008","journal-title":"Diabetologia"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4290","DOI":"10.1128\/IAI.00255-08","article-title":"Streptozocin-induced diabetic mouse model of urinary tract infection","volume":"76","author":"Rosen","year":"2008","journal-title":"Infect. Immun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"ftv002","DOI":"10.1093\/femspd\/ftv002","article-title":"Impaired cytokine expression, neutrophil infiltration and bacterial clearance in response to urinary tract infection in diabetic mice","volume":"73","author":"Ozer","year":"2015","journal-title":"Pathog. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"ftu004","DOI":"10.1093\/femspd\/ftu004","article-title":"Advanced glycation end products facilitate bacterial adherence in urinary tract infection in diabetic mice","volume":"73","author":"Ozer","year":"2015","journal-title":"Pathog. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2331","DOI":"10.2337\/db11-0159","article-title":"Immunosuppressive effects of streptozotocin-induced diabetes result in absolute lymphopenia and a relative increase of T regulatory cells","volume":"60","author":"Muller","year":"2011","journal-title":"Diabetes"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.imlet.2014.12.006","article-title":"Immunotoxicological effects of streptozotocin and alloxan: In vitro and in vivo studies","volume":"163","author":"Diab","year":"2015","journal-title":"Immunol. Lett."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Saadane, A., Lessieur, E.M., Du, Y., Liu, H., and Kern, T.S. (2020). Successful induction of diabetes in mice demonstrates no gender difference in development of early diabetic retinopathy. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0238727"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"131","DOI":"10.2174\/1573399810666140508121012","article-title":"Leptin- and leptin receptor-deficient rodent models: Relevance for human type 2 diabetes","volume":"10","author":"Wang","year":"2014","journal-title":"Curr. Diabetes Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5634","DOI":"10.1172\/JCI98595","article-title":"Insulin receptor signaling regulates renal collecting duct and intercalated cell antibacterial defenses","volume":"128","author":"Murtha","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"114007","DOI":"10.1016\/j.celrep.2024.114007","article-title":"Insulin receptor signaling engages bladder urothelial defenses that limit urinary tract infection","volume":"43","author":"Schwartz","year":"2024","journal-title":"Cell Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e2400666121","DOI":"10.1073\/pnas.2400666121","article-title":"Insulin receptor orchestrates kidney antibacterial defenses","volume":"121","author":"Schwartz","year":"2024","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1111\/dom.15981","article-title":"Analysing the influence of dapagliflozin on urinary tract infection vulnerability and kidney injury in mice infected with uropathogenic Escherichia coli","volume":"27","author":"Salamon","year":"2025","journal-title":"Diabetes Obes. Metab."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1111\/dom.14064","article-title":"Hyperglucosuria induced by dapagliflozin augments bacterial colonization in the murine urinary tract","volume":"22","author":"Saenkham","year":"2020","journal-title":"Diabetes Obes. Metab."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e0017226","DOI":"10.1128\/iai.00172-26","article-title":"Diabetes and hyperglucosuria exacerbate the severity of urinary tract infection caused by uropathogenic E. coli in the mouse model","volume":"94","author":"Neupane","year":"2026","journal-title":"Infect. Immun."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Paudel, S., John, P.P., Poorbaghi, S.L., Randis, T.M., and Kulkarni, R. (2022). Systematic Review of Literature Examining Bacterial Urinary Tract Infections in Diabetes. J. Diabetes Res., 3588297.","DOI":"10.1155\/2022\/3588297"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/genomeA.01338-14","article-title":"Complete Genome Sequence of Streptococcus agalactiae CNCTC 10\/84, a Hypervirulent Sequence Type 26 Strain","volume":"2","author":"Hooven","year":"2014","journal-title":"Genome Announc."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bcp.2015.08.108","article-title":"Animal models for diabetes: Understanding the pathogenesis and finding new treatments","volume":"99","author":"King","year":"2016","journal-title":"Biochem. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1038\/nature18285","article-title":"Accounting for reciprocal host-microbiome interactions in experimental science","volume":"534","author":"Stappenbeck","year":"2016","journal-title":"Nature"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3588","DOI":"10.1128\/IAI.00122-11","article-title":"Immune activation and suppression by group B streptococcus in a murine model of urinary tract infection","volume":"79","author":"Kline","year":"2011","journal-title":"Infect. Immun."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Kulkarni, R., Randis, T.M., Antala, S., Wang, A., Amaral, F.E., and Ratner, A.J. (2013). beta-Hemolysin\/cytolysin of Group B Streptococcus enhances host inflammation but is dispensable for establishment of urinary tract infection. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0059091"}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/15\/9\/923\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T12:59:02Z","timestamp":1788267542000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/15\/9\/923"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,1]]},"references-count":38,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["pathogens15090923"],"URL":"https:\/\/doi.org\/10.3390\/pathogens15090923","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,1]]}}}