Characterization of Mycobacterium orygis, Mycobacterium bovis, and Mycobacterium caprae Infections in Humans in Western Canada.

Epidemiologic research on zoonotic tuberculosis historically used Mycobacterium bovis as a surrogate measure, however, increased reports of human tuberculosis caused by other animal-associated Mycobacterium tuberculosis complex members like Mycobacterium orygis necessitates their inclusion. We performed a retrospective cohort study including persons infected with any animal-lineage M. tuberculosis complex species in Alberta, Canada, from January 1995 to July 2021, identifying 42 patients (20 M. bovis, 21 M. orygis, one M. caprae). Demographic, epidemiologic and clinical characteristics were compared against persons with culture-confirmed M. tuberculosis infection. The proportion of culture-positive infections caused by M. orygis increased continuously from 2016-2020. Significantly more females at a higher median age were impacted by M. orygis, with all patients originating from South Asia. M. bovis caused significantly more extra-pulmonary disease, and disproportionately impacted young females, particularly those pregnant or post-partum. All infections were acquired abroad. These findings can aid in developing targeted public health interventions.

Disseminated cutaneous Mycobacterium chelonae infection secondary to an indwelling catheter in an immunocompetent host.

Background: Mycobacterium chelonae is a species of nontuberculous mycobacteria that typically causes localized cutaneous disease in immunocompetent hosts. There have been few reports of disseminated infections in immunocompetent individuals which have often been associated with invasive medical procedures. Case Presentation: In this report, we describe a 43-year-old immunocompetent female with an implanted venous access device who presented with skin lesions increasing in size and frequency over the course of five months despite antimicrobial therapy. A diagnosis was not made until mycobacterial culture from a skin biopsy grew M. chelonae. Conclusion: Disseminated cutaneous M. chelonae infection can be a rare complication of indwelling venous catheterization among immunocompetent patients.

Rapid Unmasking of Immune-related Adverse Events After Discontinuation of Chemotherapy in Chemo-immunotherapy Regimens.

Pembrolizumab is an immune-checkpoint inhibitor (ICI) of programmed cell death protein 1 (PD-1), which restores T-cell-mediated antitumor immune activity and therefore enhances the body's immune response to cancer cells. Due to the nature of this therapy, immune-related adverse events (irAE) can manifest in nearly every organ system. Chemo-immunotherapy regimens are now considered first-line treatment for several cancers, with recent literature suggesting there are higher rates of certain irAEs with ICI monotherapy when compared with chemo-immunotherapy combinations. In certain regimens chemo-immunotherapy induction is followed by ICI maintenance monotherapy, and data regarding irAE incidence in this transition period are very limited. We report 3 cases of patients on pembrolizumab in combination with cytotoxic chemotherapy who developed an irAE shortly following discontinuation of a chemotherapy agent. Cases were identified in the Rheumatology in Immuno-Oncology clinic at the University of Alberta and clinical data were extracted by retrospective chart review after obtaining written consent from individual patients. These findings demonstrate that chemotherapy may suppress irAEs in patients using ICIs, and that when chemotherapy agents in combined regimens are discontinued, irAEs can be "unmasked" within the following 6 weeks. Clinicians should be aware of this risk and monitor for irAE development during this critical time period. To the best of the authors' knowledge, this has not been previously reported in the literature.

Fluorine-19 NMR spectroscopy of fluorinated analogs of tritrpticin highlights a distinct role for Tyr residues in antimicrobial peptides.

Because of their potential as novel antibiotic agents, antimicrobial peptides (AMPs) have generated considerable interest. The mechanism of bacterial toxicity of AMPs often involves the disruption and/or permeabilization of the bacterial membrane; even those that act intracellularly first have to traverse the membrane. In this work we have explored the incorporation of the fluorinated aromatic amino acids fluoro-Phe and fluoro-Tyr into the Trp- and Arg-rich AMP tritrpticin, and investigated their role in the membrane binding properties and the antimicrobial activity of the peptide. Fluorinated peptides were obtained with good yield by recombinant expression of tritrpticin as a calmodulin-fusion protein in Escherichia coli. Cells were grown in the presence of glyphosate, an inhibitor of aromatic amino acid biosynthesis, and the peptides were released by proteolysis from the purified fusion protein. By using SDS micelles, as a simplified model of the bacterial cytoplasmic membrane, we could study the peptide-membrane interactions and the preferred location of individual fluorinated residues in the micelles by 19F NMR spectroscopy. Solvent-perturbation 19F NMR measurements revealed that para-fluoro-Phe residues are embedded deeply in the hydrophobic region of the micelles. On the other hand, 3-fluoro-Tyr residues introduced in tritrpticin were located near the surface of the micelles with high solvent exposure, while 2-fluoro-Tyr sidechains were less solvent exposed. In combination with the outcome of determinations of their antimicrobial activity, our 19F NMR results indicate that the higher solvent exposure of Tyr residues correlates with a decrease of the antimicrobial potency. This different role of Tyr can likely be extended from tritrpticin to other cationic AMPs.