TUBERCULOMA CASEOUS NECROSIS-DERIVED BACTERIA (CORYNEBACTERIUM AND STAPHYLOCOCCUS) ENHANCE GRANULOMA FORMATION IN VITRO AND STIMULATE MYCOBACTERIAL BIOFILM DEVELOPMENT
- Authors: Orlova E.A.1, Ogarkov O.B.1, Schwartz Y.S.2, Lykov A.P.3, Nemkova E.K.2
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Affiliations:
- FSBSI Scientific Center for Family Health and Human Reproduction Problems
- FSBI Novosibirsk Tuberculosis Research Institute of the Ministry of Health RF
- IC&G SB RAS
- Section: SHORT COMMUNICATIONS
- Submitted: 25.08.2025
- Accepted: 07.10.2025
- URL: https://iimmun.ru/iimm/article/view/17999
- DOI: https://doi.org/10.15789/2220-7619-TCN-17999
- ID: 17999
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Abstract
Granuloma formation represents one of the key stages in tuberculosis pathogenesis, characterized by the development of specialized cellular structures surrounding Mycobacterium tuberculosis within foci. These structures are presented by complex, multicomponent assemblies that both detain the pathogen and simultaneously serve as a niche for its persistence. It has been firmly established that the mycobacterial cord factor is an important driver of granuloma induction, being involved in intercellular interactions and the organization of granuloma three-dimensional scaffold. However, the influence of the resident microbiota on this process, as well as its contribution to the formation of mycobacterial biofilms, remains understudied. This work investigates an effect of Corynebacterium kefirresidentii and Staphylococcus epidermidis lysates (isolated from tuberculoma-related caseous necrosis) on in vitro granuloma formation using C57BL/6 mouse peritoneal macrophages and splenocytes. Additionally, an influence of C. kefirresidentii on vaccine strain M. bovis BCG growth and biofilm development was examined. The study demonstrates that C. kefirresidentii induces the formation of a rapidly growing M. bovis BCG biofilm with characteristic cord-like architecture and a prominent extracellular matrix. This effect was accompanied by a statistically significantly expanded area under the growth curve compared to the control (p < 0.0001). Co-cultivation experiments with the clinical strain M. tuberculosis Beijing B0/W148 and bacterial lysates revealed limited antimycobacterial activity but demonstrated a pronounced stimulatory effect on the formation of granuloma-like structures in the M. tuberculosis-induced in vitro granulemogenesis model. C. kefirresidentii and S. epidermidis lysates significantly propagated granuloma formation as evidenced by markedly increased both cellular aggregate number and size (p < 0.01), including the formation of large clusters containing more than 50 cells. Taken together, these findings suggest that satellite pathobiota derived from caseous necrosis of tuberculous foci might be involved in modulating key mechanisms of infection pathogenesis and point at its potential contribution to unfavorable outcomes in pulmonary tuberculosis.
Keywords
About the authors
Elizaveta A. Orlova
FSBSI Scientific Center for Family Health and Human Reproduction Problems
Email: elizaveta.a.orlova@gmail.com
ORCID iD: 0000-0003-2169-0242
SPIN-code: 5258-4087
Scopus Author ID: 57223019914
ResearcherId: ABC-3428-2020
Junior Researcher at the Laboratory of Epidemic and Social Infections of the Institute of Epidemiology and Microbiology
Россия, 16 Timiryazeva St, Irkutsk, 664003, RussiaOleg B. Ogarkov
FSBSI Scientific Center for Family Health and Human Reproduction Problems
Email: obogarkov@mail.ru
ORCID iD: 0000-0002-3168-1983
SPIN-code: 1956-2888
Scopus Author ID: 6603264302
ResearcherId: G-6966-2011
Doctor of Medical Sciences, Head of the Institute of Epidemiology and Microbiology of the FSBSI SС FHHRP
Россия, 664003, Russian Federation, Irkutsk, Timiryazeva st., 16Yakov Sh. Schwartz
FSBI Novosibirsk Tuberculosis Research Institute of the Ministry of Health RF
Email: yshschwartz@mail.ru
ORCID iD: 0000-0002-3036-9795
SPIN-code: 4312-8550
Scopus Author ID: 36867506300
MD, Doctor of Medical Sciences, Deputy Director for Science
Россия, 630040, Russian Federation, Novosibirsk, Okhotskaya St. 81 AAlexander P. Lykov
IC&G SB RAS
Email: aplykov2@mail.ru
ORCID iD: 0000-0003-4897-8676
Scopus Author ID: 7005078523
MD, Doctor of Medical Sciences, Leading Researcher at the Laboratory of Cellular Technologies
Россия, 630117, Russian Federation, Novosibirsk, Arbuzova st., 6Elizaveta K. Nemkova
FSBI Novosibirsk Tuberculosis Research Institute of the Ministry of Health RF
Author for correspondence.
Email: elizaveta.nemkova@mail.ru
ORCID iD: 0000-0003-2724-9546
Scopus Author ID: 57288209600
Junior Researcher at the Department of Applied Scientific Research
Россия, 630040, Russian Federation, Novosibirsk, Okhotskaya St. 81 AReferences
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