Karl Ocius

Gut Microbes. 2026 Dec 31;18(1):2617694. doi: 10.1080/19490976.2026.2617694. Epub 2026 Jan 26.

ABSTRACT

Systemic infections are a common cause of complications and death after stroke. These infections can occur due to the breakdown of the gut epithelial barrier and the translocation of bacteria from the gut to peripheral systemic tissues. However, it remains unclear whether gut bacteria also translocate to the brain and contribute to stroke-induced neuronal damage. In this study, we observed a significant number of peptidoglycan- and lipopolysaccharide-positive bacteria in the ischemic hemisphere of mice subjected to either photothrombotic (PT) stroke or middle cerebral artery occlusion (MCAO). In contrast, no bacteria were observed in the ischemic brains of germ-free mice following MCAO. Absolute quantification via PCR also revealed increased bacteria in the ischemic hemisphere and blood of PT mice. Bacterial translocation to the brain is associated with the breakdown of the gut-epithelial and blood-brain barriers. Although inhibition of sympathetic tone reduces gut-epithelial barrier permeability, the bacterial load in the brain and functional deficits poststroke, it does not affect cerebral apoptosis, neuroinflammation or infarct volume. Collectively, these findings indicate that activation of the sympathetic nervous system after stroke promotes the migration of gut-derived bacteria into the ischemic brain, and this process worsens motor function in mice.

PMID:41586772 | PMC:PMC12851396 | DOI:10.1080/19490976.2026.2617694

BMC Microbiol. 2026 Jan 23. doi: 10.1186/s12866-026-04722-4. Online ahead of print.

NO ABSTRACT

PMID:41578181 | DOI:10.1186/s12866-026-04722-4

bioRxiv [Preprint]. 2025 Dec 4:2025.12.03.691670. doi: 10.64898/2025.12.03.691670.

ABSTRACT

The immune system has developed specialized mechanisms to recognize intracellular pathogens such as Mycobacterium tuberculosis (Mtb). Major Histocompatibility Complex Class I-Related molecule (MR1) is a conserved nonclassical antigen presenting molecule that presents ligands derived from microbial riboflavin synthesis to Mucosal Associated Invariant T (MAIT) cells. While endosomal trafficking facilitates MR1 antigen presentation during Mtb infection, the exact mechanisms by which MR1 loading of Mtb-derived ligands occurs are not known. We found that trafficking through sorting endosomes mediates MR1 antigen presentation during Mtb infection. Sorting endosomes utilize trafficking proteins such as Syntaxin 6, Syntaxin 12, Syntaxin 16 and VAMP4. Prior work demonstrates the importance of VAMP4 for MR1 presentation during Mtb infection; we have found that Stx12 and Stx16 are also important. Interference with Stx12 or Stx16 via siRNA-mediated knockdown reduces MR1 antigen presentation of Mtb. Using RFP-tagged constructs, we found Stx16 co-localized more with MR1 vesicles compared to Stx12 in MR1-GFP expressing airway epithelial cells. Stx12 and Stx16 blockade increase MR1 surface stabilization and total expression, indicating that impaired endosomal trafficking hinders MR1 internalization. Together, these findings support a role for sorting endosomes in the selective sampling of the intracellular environment and MR1-mediated recognition of Mtb-infected cells.

PMID:41573916 | PMC:PMC12822724 | DOI:10.64898/2025.12.03.691670

PLoS Pathog. 2026 Jan 20;22(1):e1013849. doi: 10.1371/journal.ppat.1013849. eCollection 2026 Jan.

ABSTRACT

Lyme disease is a vector-borne illness transmitted by infected Ixodes spp. ticks. Dissemination of the Lyme spirochete-Borrelia burgdorferi-from the tick bite site results in a bi-phasic infection; the latter phase can cause severe musculoskeletal disease including arthritis. Lyme arthritis is an inflammatory disorder and maladaptive immune response to B. burgdorferi infection and its cellular products. One such product, which has been implicated as a key mediator of Lyme arthritis, is peptidoglycan. Peptidoglycan (PG) is a near ubiquitous feature of the bacterial cell envelope, but several chemical features make B. burgdorferi PG distinct from other members of the kingdom. We hypothesized the overall chemical composition and structural architecture of the B. burgdorferi cell wall are essential to Lyme disease pathogenesis. To manipulate the PG peptide chemical composition, as well as the native cross-links, we produced an isogenic deletion of a putative PG carboxypeptidase dacA homologue and assessed both the molecular and cellular phenotypes while probing the pathogenicity of our mutant strain. Our combined and comprehensive approach indicates while changes to PG stem peptide and cross-linking have virtually no discernable impact on any B. burgdorferi characteristic in vitro, alterations have significant impacts on tissue tropism and result in a near complete attenuation of Lyme arthritis. PG sacculi containing increased amounts of free and cross-linked pentapeptide surprisingly caused the disassociation of p83/100, an abundant periplasmic protein of unknown function previously implicated in joint tropism, likely contributing to a marked decrease in pathogenicity. These studies strengthen our understanding of the B. burgdorferi cell envelope, its unusual components, and further define bacterial features that mediate infectious arthritis.

PMID:41557633 | PMC:PMC12818604 | DOI:10.1371/journal.ppat.1013849

Nat Commun. 2026 Jan 13;17(1):231. doi: 10.1038/s41467-025-67099-4.

ABSTRACT

Mammals regulate the localization, composition, and activity of their native microbiota at colonization sites. Lectins residing at these sites influence microbial populations, but their functional roles are often unclear. Intelectins are found in chordates at mucosal barriers, but their functions are not well characterized. In this study, we find that mouse intelectin-2 (mItln2) and human intelectin-2 (hItln2) engage and crosslink mucins via carbohydrate recognition. Moreover, both lectins recognize microbes within native microbial communities, including gram-positive and gram-negative isolates from the respiratory and gastrointestinal tracts. This ability to engage mammalian and microbial glycans arises from calcium-coordinated binding of carbohydrate residues within mucus and microbial surfaces. Microbes, but not human cells, bound by mItln2 or hItln2, suffer a loss of viability. These findings underscore the crucial antimicrobial role of mammalian intelectin-2 in mucosal defense, where it plays offensive (microbial killing) and defensive (mucus crosslinking) roles in regulating microbial colonization.

PMID:41530121 | PMC:PMC12800186 | DOI:10.1038/s41467-025-67099-4

Proc Natl Acad Sci U S A. 2026 Jan 20;123(3):e2519608123. doi: 10.1073/pnas.2519608123. Epub 2026 Jan 16.

ABSTRACT

Unlike commonly studied rod-shaped bacteria, mycobacteria grow from their poles, requiring precise coordination between division and initiation of new pole growth. The mechanisms that mediate this transition are largely unknown, but likely represent a rich source of drug targets for the treatment of mycobacterial infections, including tuberculosis. Here, we identify TapA (MSMEG_3748/Rv1697) as a key regulator of this transition. TapA interacts with the sensor kinase MtrB at the septum to initiate a signaling cascade that ultimately results in the expression of the essential peptidoglycan hydrolases RipAB, among others, at the end of division. Loss of TapA disrupts division, dysregulates pole formation, and sensitizes Mycobacterium tuberculosis and other mycobacteria to several first and second-line TB antibiotics, establishing TapA as a potential therapeutic target, and defining a link between cell cycle progression, envelope remodeling, and intrinsic antibiotic resistance in mycobacteria.

PMID:41543900 | PMC:PMC12818412 | DOI:10.1073/pnas.2519608123

Access Microbiol. 2025 Dec 19;7(12):001074.v4. doi: 10.1099/acmi.0.001074.v4. eCollection 2025.

ABSTRACT

Proteins facilitating bacterial cell wall (CW) biosynthesis are crucial for survival and broadly remain the target of numerous antimicrobial agents. Herein, we focused on characterizing the physiological roles of low-molecular-weight penicillin-binding proteins (LMW PBPs), with dd-carboxypeptidase (dd-CPase) activity, in Mycobacterium smegmatis. Following various combinatorial gene deletions, cell viability, colony structure and the ability to produce biofilms remained unperturbed. Whilst small changes in cellular morphology and permeability were evident, hierarchical roles could not be ascribed to specific dd-CPase homologues. Strains exposed to lysozyme exhibited low levels of compensatory expression for the remaining homologues, but this was not evident for exposure to the CW-targeting Augmentin. When tested against a broader concentration range of various antibiotics, using MIC and spotting assays, only marginal changes in drug susceptibility were evident. Strains cultured under conditions of excess NaCl or enhanced pH levels grew normally. Given the established role of remodelling in dd-CPase enzymes of other bacteria, we further assessed whether the ability to repair lysozyme-induced CW damage was compromised. With the incorporation of the fluorescent d-amino acid peptidoglycan probe, TAMRA-d-alanine, as a proxy for remodelling, no changes in staining patterns were evident. However, the frequency of cells containing unresolved septa increased in all mutant strains, suggesting a potential role for dd-CPases in the mycobacterial cell process. In conclusion, we have demonstrated that the combinatorial deletion of non-essential mycobacterial dd-CPase homologues largely has no significant impact on mycobacterial physiology or involvement in the response to the various environmental stressors tested herein.

PMID:41532140 | PMC:PMC12795238 | DOI:10.1099/acmi.0.001074.v4