Background: We have previously reported that ATP treatment of M bovis-BCG infected human macrophages induces P2X₇ receptor-dependent killing of intracellular mycobacteria. The mechanism mediating this bactericidal effect has not been full characterized but is known to be Ca²⁺-dependent and to promote the maturation and acidification of mycobacteria-containing phagosomes. In this study we demonstrate that the ATP/P2X₇-mediated, mycobactericidal effect also involves the induction of cell autophagy. Results: We report that 3 mM ATP induces rapid cell autophagy in THP1 cells and monocyte-derived macrophages within 30 minutes post-treatment, as revealed by the expression of LC3-II bands on western blot analysis. Using Ca²⁺-free media and selective P2X₇ agonists and antagonists, ATP-induced cell autophagy was shown to be Ca²⁺ and P2X₇ receptor-dependent. Electron microscopy of ATP-treated, BCG-infected MDMs revealed the presence of the bacteria within characteristic double-membraned autophagosomes. Confocal analysis further confirmed that pharmacological inhibition of autophagy by wortmannin or pre-treatment of macrophages with anti-P2X₇ antibody blocked ATP-induced phago-lysosomal fusion. Induction of cell autophagy with ATP was also temporally associated with a fall in intracellular mycobacterial viability, which was suppressed by treatment with wortmannin or the selective P2X₇ antagonist, oxidized ATP (oATP). Conclusion: We provide the first evidence that ATP/P2X₇-mediated killing of intracellular mycobacteria involves the induction of cell autophagy. The findings support the hypothesis that autophagy plays a key role in the control of mycobacterial infections.

From March to June 2021, India experienced a deadly second wave of COVID-19, with an increased number of post-vaccination breakthrough infections reported across the country. To understand the possible reason for these breakthroughs, we collected 677 clinical samples (throat swab/nasal swabs) of individuals from 17 states/Union Territories of the country who had received two doses (n = 592) and one dose (n = 85) of vaccines and tested positive for COVID-19. These cases were telephonically interviewed and clinical data were analyzed. A total of 511 SARS-CoV-2 genomes were recovered with genome coverage of higher than 98% from both groups. Analysis of both groups determined that 86.69% (n = 443) of them belonged to the Delta variant, along with Alpha, Kappa, Delta AY.1, and Delta AY.2. The Delta variant clustered into four distinct sub-lineages. Sub-lineage I had mutations in ORF1ab A1306S, P2046L, P2287S, V2930L, T3255I, T3446A, G5063S, P5401L, and A6319V, and in N G215C; Sub-lineage II had mutations in ORF1ab P309L, A3209V, V3718A, G5063S, P5401L, and ORF7a L116F; Sub-lineage III had mutations in ORF1ab A3209V, V3718A, T3750I, G5063S, and P5401L and in spike A222V; Sub-lineage IV had mutations in ORF1ab P309L, D2980N, and F3138S and spike K77T. This study indicates that majority of the breakthrough COVID-19 clinical cases were infected with the Delta variant, and only 9.8% cases required hospitalization, while fatality was observed in only 0.4% cases. This clearly suggests that the vaccination does provide reduction in hospital admission and mortality.

Viral infections are a major threat to the human population due to the lack of selective therapeutic measures. The morbidity and mortality reported worldwide are very alarming against viral pathogens. The proinflammatory environment is required for viral inhibition by initiating the host immune response. The host immune response fights these pathogens by secreting different cytokines. Interleukin‐17 (IL‐17) a proinflammatory cytokine mainly produced by T helper type 17 cells, plays a vital role in the regulation of host immune response against various pathogens, including viruses. However, dysregulated production of IL‐17 induces chronic inflammation, autoimmune disorders, and may lead to cancer. Recent studies suggest that IL‐17 is not only involved in the antiviral immune response but also promotes virus‐mediated illnesses. In this review, we discuss the protective and pathogenic role of IL‐17 against various viral infections. A detailed understanding of IL‐17 during viral infections could contribute to improve therapeutic measures and enable the development of an efficient and safe IL‐17 based immunotherapy.

In view of the role of TLR2 activation in host defense against mycobacteria, the present study was conducted to examine whether TLR2 polymorphisms could account for the increased prevalence of tuberculosis in Indian patients. Detection of such polymorphisms would help in assessing the risk of developing active tuberculosis among contacts or HIV positive patients and in identifying candidates for chemoprophylaxis.

The number of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) cases is increasing in India. This study looks upon the geographic distribution of the virus clades and variants circulating in different parts of India between January and August 2020. The NPS/OPS from representative positive cases from different states and union territories in India were collected every month through the VRDLs in the country and analyzed using next-generation sequencing. Epidemiological analysis of the 689 SARS-CoV-2 clinical samples revealed GH and GR to be the predominant clades circulating in different states in India. The northern part of India largely reported the ‘GH’ clade, whereas the southern part reported the ‘GR’, with a few exceptions. These sequences also revealed the presence of single independent mutations—E484Q and N440K—from Maharashtra (first observed in March 2020) and Southern Indian States (first observed in May 2020), respectively. Furthermore, this study indicates that the SARS-CoV-2 variant (VOC, VUI, variant of high consequence and double mutant) was not observed during the early phase of virus transmission (January–August). This increased number of variations observed within a short timeframe across the globe suggests virus evolution, which can be a step towards enhanced host adaptation.

A high prevalence of antimicrobial resistance among urinary isolates in the Garhwal region of Uttaranchal. To identify the most appropriate antibiotic for empirical treatment of community-acquired acute cystitis on the basis of local antimicrobial sensitivity profile. A prospective clinico-microbiological study including all clinically diagnosed patients with community acquired acute cystitis attending a tertiary care teaching hospital over a period of three years. Clean-catch midstream urine specimens, from 524 non-pregnant women with community-acquired acute cystitis, were subjected to semi-quantitative culture and antibiotic susceptibility by the Kirby- Bauer disc diffusion method. A survey was also conducted on 30 randomly selected local practitioners, to know the prevalent prescribing habits in this condition. The difference between the susceptibility rates of E. coli isolates to Nitrofurantoin and the other commonly prescribed antibiotics was analysed by applying the z test for proportion. 354 (67.5%) specimens yielded significant growth of E. coli.> 35% of the urinary E.coli isolates were resistant to the fluoroquinolones, which were found to be the most commonly used empirical antibiotics in acute cystitis. Resistance was minimum against Nitrofurantoin (9.3%, 33) and Amikacin (11.0%,39).> 80% of the fluoroquinolone-resistant strains were found to be sensitive to Nitrofurantoin. The best in vitro susceptibility profile in our study has been shown by Nitrofurantoin and a significantly high proportion of the urinary E. coli isolates have already developed resistance to the currently prescribed empirical antibiotics, viz. the fluoroquinolones. In view of these in vitro susceptibility patterns, a transition in empirical therapy appears imminent.