Novel Mutations in MPT64 Secretory Protein of Mycobacterium tuberculosis Complex.

Tuberculosis (TB) is a global health problem caused by the Mycobacterium tuberculosis complex (MTBC). These bacteria secrete various proteins involved in the pathogenesis and persistence of MTBC. Among the secretory proteins, MPT64 (Rv1980C) is highly conserved and is also known as a major culture filtrate that is used in rapid diagnosis of MTBC. In the current study, we aimed to find the mutation in this highly conserved protein in isolates from the Pashtun-dominant province of Pakistan. We analyzed 470 M. tuberculosis whole-genome sequences of Khyber Pakhtunkhwa Province. Mutations in the MPT64 gene were screened through TB-Profiler and BioEdit software tools. The DynaMut web server was used to analyze the impact of the mutation on protein dynamics and stability. Among 470 MTB genomes, three non-synonymous mutations were detected in nine isolates, and one synonymous mutation (G208A) was found in four isolates. Mutation G211T (F159L), which was detected at the C-terminal domain of the protein in six isolates, was the most prominent. The second novel mutation, T480C (I70V), was detected in two isolates at the C-terminal side of the protein structure. The third novel mutation, A491C (L66R), was detected in a single isolate at the N-terminal side of the MPT64 protein. The effect of these three mutations was destabilizing on the protein structure. The molecular flexibility of the first two mutations increased, and the last one decreased. MPT64 is a highly conserved secretory protein, harboring only a few mutations. This study provides useful information for better managing the diagnosis of MTB isolates in high TB-burden countries.

Physicians' Perception About the Side Effects of COVID-19 Vaccine and Their Role in Vaccination Program.

INTRODUCTION: The Coronavirus disease 2019 (COVID-19) caused many problems in the health sector. Effective and safe vaccines are the only tool to combat the COVID-19 disease. Researchers and regulatory agencies have made efforts to develop such vaccines and healthcare professionals were prioritized for the vaccination program as first-line care providers. Considering this prioritization, we aimed to assess the physicians' perceptions regarding the side effects of the COVID-19 vaccine. METHODS: An interview-based study was conducted from May 5 May to November 5, 2021 (6 months) in a teaching hospital in the capital city of Islamabad, Pakistan. RESULTS: Among the 200 physicians who agreed to participate in the interview, 74% were male. A total of 94% did not experience any side effects after receiving the COVID-19 vaccine, regardless of the type of vaccine; 6% experienced side effects. Furthermore, 90% of physicians were afraid of side effects due to the high number of vaccine doses. CONCLUSION: Conclusively, physicians had a positive perception regarding the COVID-19 vaccine. Healthcare authorities and related departments must take precautions to ensure the effective and safe COVID-19 vaccine to change the perceptions of physicians who had a negative perception. This will not only reduce the reluctance among physicians regarding administering COVID-19 vaccine, but will also boost and facilitate the vaccination program for the general public as well.

Loss of Jak2 protects cardiac allografts from chronic rejection by attenuating Th1 response along with increased regulatory T cells.

Chronic rejection acts as the most formidable obstacle for organ transplantation in clinical settings. Herein we demonstrated in a cardiac transplantation model that blockade of Janus kinase 2 (Jak2) provides protection for cardiac allografts against chronic rejection. Specifically, loss of Jak2 almost completely abolished the production of IFN-γ+ Th1 cells, while the percentage of Foxp3+ regulatory T cells (Tregs) was significantly increased. As a result, loss of Jak2 significantly prolonged allograft survival (58 ± 30.6 days vs. 7 ± 0.3 days). Particularly, 4 out of 13 Jak2 deficient recipients (30%) showed long-term acceptance of allografts as manifested by the graft survival time > 100 days. Cellular studies revealed that Jak2 deficiency did not impact the intrinsic proliferative capability for CD4+ T cells in response to nonspecific polyclonal and allogenic stimulation. Mechanistic studies documented that the impaired Th1 development was caused by the attenuated IFN-γ/STAT1 and IL-12/STAT4 signaling along with repressed expression of Th1 transcription factors T-bet, Hlx and Runx3. However, the IL-2/STAT5 signaling remained intact, which ensured normal Treg development in Jak2-/- naïve CD4 T cells. Together, our data support that blockade of Jak2 may have therapeutic potential for prevention and treatment of allograft rejection in clinical settings.