HIV is identified as a factor that aggravates tuberculosis disease pathogenesis and its progression to latent TB. While, TB is declared as one of the major causes for AIDS-associated mortality. So there is a dire need for new drugs to combat such ailments that have a synergistic interaction.This has led us to study a novel antibiotic purified from a marine Streptomyces sp isolated from the coral reef ecosystem of South Indian coast. Streptomyces sp. R2 (MTCC 5597; DSM 26035)., isolated from the marine water was grown on agar plates and the crude yellowish orange pigment secreted was extracted using various solvents. The antibiotic, named as Transitmycin, was purified and tested against M. tuberculosis, drug resistant strains, and M. tuberculosis biofilm. The compound was also tested against HIV-1 viruses belonging to six subtypes.  Several characterisation tools were used to elucidate the structure of this novel antibiotic. Transitmycin was derivitaised to elucidate the absolute configurations of the amino acids present in it. Tr, unlike actinomycin D, has L-valine in both the rings instead of D-valine (found in the latter). Also, one of the proline in Tr is in D–configuration while it is in L configuration in actinomycin D suggesting that ours is a novel compound and is not reported so far. It exhibits dual activities against the standard H37Rv, 49 drug sensitive clinical isolates, and MtB biofilm as well as standard and 20 clinical isolates of HIV. This is the first paper that reports the isolation of a new antibiotic from marine actinobacteria exhibiting unusual anti-TB and HIV activities which could be exploited further as a lead molecule in the quest for the design of drug with dual activities.### Competing Interest StatementThe authors have declared no competing interest.### Funding StatementYes### Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:Donor PBMC were obtained from healthy volunteers after obtaining the approval of the Institutional Ethics Committee of the National Institute for Research in Tuberculosis as well as the informed consent of the participants.I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.YesSUPPORTINg information

Marine-derived actinobacteria have tremendous potential to produce novel metabolites with diverse biological activities. The Andaman coast of India has a lot of microbial diversity, but it is still a relatively unknown ecology for isolating novel actinobacteria with beneficial bioactive compounds. We have isolated 568 actinobacterial strains from mangrove rhizosphere sediments and sponge samples. Crude extracts from 75 distinct strains were produced by agar surface fermentation and extracted using ethyl acetate. In the disc diffusion method, 25 actinobacterial strains showed antimicrobial activity; notably, the strain MAB56 demonstrated promising broad-spectrum activity. Strain MAB56 was identified as Streptomyces albus by cultural, microscopic, and molecular methods. Conditions for bioactive metabolites from MAB56 were optimized and produced in a lab-scale fermenter. Three active metabolites (C1, C2, and C3) that showed promising broad-spectrum antimicrobial activity were isolated through HPLC-based purification. Based on the UV, FT-IR, NMR, and LC–MS analysis, the chemical nature of the active compounds was confirmed as 12-methyltetradecanoic acid (C1), palmitic acid (C2), and tridecanoic acid (C3) with molecular formulae C14H28O2, C16H32O2, and C13H26O2, respectively. Interestingly, palmitic acid (C2) also exhibited anti-HIV activity with an IC50 value of < 1 µg/ml. Our findings reveal that the actinobacteria from the Andaman marine ecosystems are promising for isolating anti-infective metabolites.

This study involves the in-vitro and in-vivo anti-TB potency and in-vivo safety of Transitmycin (TR) (PubChem CID:90659753)- identified to be a novel secondary metabolite derived from Streptomyces sp (R2). TR was tested in-vitro against drug resistant TB clinical isolates (n = 49). 94% of DR-TB strains (n = 49) were inhibited by TR at 10μg ml-1. In-vivo safety and efficacy studies showed that 0.005mg kg-1 of TR is toxic to mice, rats and guinea pigs, while 0.001mg kg-1 is safe, infection load did not reduce. TR is a potent DNA intercalator and also targets RecA and methionine aminopeptidases of Mycobacterium. Analogue 47 of TR was designed using in-silico based molecule detoxification approaches and SAR analysis. The multiple targeting nature of the TR brightens the chances of the analogues of TR to be a potent TB therapeutic molecule even though the parental compound is toxic. Analog 47 of TR is proposed to have non-DNA intercalating property and lesser in-vivo toxicity with high functional potency. This study attempts to develop a novel anti-TB molecule from microbial sources. Though the parental compound is toxic, its analogs are designed to be safe through in-silico approaches. However, further laboratory validations on this claim need to be carried out before labelling it as a promising anti-TB molecule.

Piriformis syndrome is a rare cause of sciatica, which results in low backache due to sciatic nerve compression. This syndrome is associated with abnormalities in the piriformis muscle, which cause sciatic nerve entrapment, like anatomical variations, muscle hypertrophy, and inflammation. It can also result from the abnormal course of sciatic nerve itself through normal piriformis muscle. Piriformis syndrome due to pyomyositis of the piriformis muscle is extremely rare and only 23 cases are reported in literature. Herein, we report one such rare case of a patient, with pyomyositis of piriformis muscle, who presented with piriformis syndrome.

Green synthesis of silver chloride nanoparticles ( AgCl NPs ) using commercial yeast extract has been carried out. The physico–chemical characterizations of AgCl NPs were carried out by UV–visible spectroscopy, XRD, FTIR, HR-SEM equipped with EDAX and TEM. In vitro efficacy of anti-mycobacterial properties of AgCl NPs were determined by agar well diffusion and Luciferase Reporter Phage (LRP) assay were used against Mycobacterium smegmatis (MC 2 155) and Mycobacterium tuberculosis H37Rv respectively. This shows that the AgCl NPs have potential anti-myobacterial activity against Mycobacterium tuberculosis H37Rv.

Tuberculosis (TB) is a contagious airborne disease caused by a bacterium, Mycobacterium tuberculosis (MTB). Emergence of multi drug resistant (MDR) and extensively drug resistance (XDR) among M. tuberculosis strains urged the situation to discovery novel anti TB antibiotics. Many assays were developed based on the whole cell and target, but each having some limitations. Being a slow grower as well as air borne pathogen, adopting suitable assay for anti TB screening is challenging. Here, we discussed about the employment of Luciferase Reporter Phage (LRP) assay for the screening of wide range of compounds against M. tuberculosis strains including drug sensitive and drug resistant strains. Literature articles published between 2006 to March 2020 in reputed journal were collected through searching web of science, pubmed and other sites. This review focus on the articles published on screening of extracts and compounds from natural products, synthetic compounds and nanoparticles from the year 2006 - March 2020 by using LRP assay. Among the whole cell assays, LRP assay provide the results in 72 hours and this assay can be used as preliminary identification of potential anti-TB compound. Hence, LRP assay is a rapid, simple and sensitive assay to screen natural molecules and synthetic compounds to determine their anti TB activity. However, limitations associated with mycobacteriophage entry into the mycobacterial cell need to be optimized to improve its sensitivity. Understanding the importance and advantages of employing LRP assay as an effective high throughput screening method helps in the significant screening of wide range of antimycobacterial agents in a relatively short time of incubation. This assay can effectively help in the development of new potential drug candidates against tuberculosis..

Tuberculosis (TB) is a contagious airborne disease caused by the pathogen, Mycobacterium tuberculosis (MTB). The conventional anti-tubercular drugs such as isoniazid and rifampicin have maximum activity and lengthy duration of therapy. The risk of serious adverse events such as hepatotoxicity, discourage both patients and providers. The big challenge here has been to find a new drug effective against TB. Lactic acid bacteria (LAB) are widely distributed in dairy products and fermented foods and also from non-dairy sources. LAB would produce novel antimicrobial peptides (bacteriocins) with unique structural characteristics and applications. The antimycobacterial properties of bacteriocins isolated from lactic acid bacteria have been studied. In this study, we isolated lactic acid bacteria from fish gut and evaluated their bacteriocins for antimycobacterial activity. Different genus of LAB was isolated and characterized viz. Pediococcus sp., Aerococcus sp, Lactobacillus sp. from fish gut. All the isolates were screened for their antibacterial and antimycobacterial activity. Based on the activity against M. smegmatis MC2155, Lactobacillus spp. (BFO21) was selected and characterized by 16S rRNA gene sequence analysis. Bacteriocin were isolated from Lactobacillus plantarum BFO21 and partially purified using chloroform solvent extraction method. About 98% of RLU reduction in terms of inhibition was found with bacteriocins of L. plantarum BFO21 against M. tuberculosis H37Rv through LRP assay. According to our results, the isolate Lactobacillus plantarum BFO21 should be evaluated for further characterization of its bacteriocins to explore their anti-tubercular activity against both replicating drug resistant M. tuberculosis and non-replicating M. tuberculosis (Latent TB)..

The present study was conducted to isolate lactic acid bacteria (LAB) from marine and mangrove sediments of East coast of India, Tamil Nadu and to evaluate their bacteriocins for antimycobacterial properties. Seventeen LAB were isolated from total of 44 marine sediment samples. Eight isolates were found to be Enterococcus sp. in which two isolates viz. LIB04 and LIB06 showed antagonistic activity against M. smegmatis Mc2155. The potent LAB isolate (LIB04) was identified as Enterococcus hirae by 16s rRNA gene sequencing analysis and named as Enterococcus hirae LIB04. The culture conditions for bacteriocins production were optimal when the medium was maintained at pH 6.5 and without NaCl for 18 hours of incubation. The activity of cell free supernatant (CFS) was completely inactivated after treatment with proteinase K. The enterocin BLIB04 were partially purified with 60% ammonium sulphate precipitation followed by methanol:chloroform extraction. The purified bacteriocin was screened for antimycobacterial activity against M. tuberculosis by luciferase reporter phage (LRP) assay. The results showed that BLIB04 effectively inhibited M. tuberculosis H37Rv, SHRE sensitive and HR resistant M tuberculosis.

Background: Mycobacterium tuberculosis, Vibrio cholerae, and pathogenic Escherichia coli are global concerns for public health. The emergence of multi-drug resistant (MDR) strains of these pathogens is creating additional challenges in controlling infections caused by these deadly bacteria. Recently, we reported that Acetate kinase (AcK) could be a broad-spectrum novel target in several bacteria including these pathogens. Methods: Here, using in silico and in vitro approaches we show that (i) AcK is an essential protein in pathogenic bacteria; (ii) natural compounds Chlorogenic acid and Pinoresinol from Piper betel and Piperidine derivative compound 6-oxopiperidine-3-carboxylic acid inhibit the growth of pathogenic E. coli and M. tuberculosis by targeting AcK with equal or higher efficacy than the currently used antibiotics; (iii) molecular modeling and docking studies show interactions between inhibitors and AcK that correlate with the experimental results; (iv) these compounds are highly effective even on MDR strains of these pathogens; (v) further, the compounds may also target bacterial two-component system proteins that help bacteria in expressing the genes related to drug resistance and virulence; and (vi) finally, all the tested compounds are predicted to have drug-like properties. Results and Conclusion: Suggesting that, these Piper betel derived compounds may be further tested for developing a novel class of broad-spectrum drugs against various common and MDR pathogens.

Tuberculosis (TB) is a communicable disease caused by Mycobacterium tuberculosis (M. tuberculosis). WHO estimated that 10.4 million new (incident) TB cases worldwide in year 2016. The increased prevalence of drug resistant strains and side effects associated with the current anti-tubercular drugs make the treatment options more complicated. Hence, there are necessities to identify new drug candidates to fight against various sub-populations of M. tuberculosis with less or no toxicity/side effects and shorter treatment duration. Bacteriocins produced by lactic acid bacteria (LAB) attract attention of researchers because of its "Generally recognized as safe" status. LAB and its bacteriocins possess an effective antimicrobial activity against various bacteria and fungi. Interestingly bacteriocins such as nisin and lacticin 3147 have shown antimycobacterial activity in vitro. As probiotics, LAB plays a vital role in promoting various health benefits including ability to modulate immune response against various infectious diseases. LAB and its metabolic products activate immune system and thereby limiting the M. tuberculosis pathogenesis. The protein and peptide engineering techniques paved the ways to obtain hybrid bacteriocin derivatives from the known peptide sequence of existing bacteriocin. In this review, we focus on the antimycobacterial property and immunomodulatory role of LAB and its metabolic products. Techniques for large scale synthesis of potential bacteriocin with multifunctional activity and enhanced stability are also discussed.

The present study was undertaken to evaluate the effect of microclimate alteration devices and feed additives on productive performance and feed intake of lactating Murrah buffaloes during summer for a period of 90 days. Twenty four early lactating Murrah buffaloes of similar body weight, parity and milk yield were selected and distributed randomly into 4 equal groups by using randomized block design (RBD). The first group T1 was provided with foggers operated daily during hot hours from 12.00 Noon to 15.00 PM, T2 with fans, T3 with fans and feed additive containing Chromisac (Chromium plus yeast) @ 500 g/ton of feed and control group without any cooling device and feed additive. The average daily dry matter intake (DMI) in T1 (15.37 ± 0.08 kg) was found to be significantly higher thanT2 (14.25 ± 0.15), T3 (14.65 ± 0.06) and control group (13.99 ± 0.11 kg).The average daily milk yield was significantly higher in T1 (10.94 ± 0.33) compared to T2, T3 and control groups, 9.55 ± 0.63, 9.78 ± 0.30 and 9.16 ± 0.36 kg, respectively. The milk constituents fat, SNF and Total solids did not differ significantly among the groups. The average daily 6% FCM yield of various experimental was found to be 12.58 ± 0.34, 10.89 ± 0.73, 11.33 ± 0.29 and 10.44 ± 0.40 percent for T1, T2, T3 and control, respectively. The use of foggers as microclimate alteration device was more advantageous over the other air circulating devices and with feed additive supplementation.

The present study conducted to know the effect of microclimate alteration devices and feed additive on re productive performance of Murrah buffaloes in summer. Total 24 Murrah buffaloes were selected. They were distributed into randomized block design (RBD) as T1 (foggers) T2 (fans), T3 (fans plus feed additive containing Chromisac (Chromium plus yeast) @ 500 g/ton of feed) and control. All the animals in groups were analysed for reproductive performance based on estrous signs, intensity of estrus, estrous response and duration of estrus. The present study revealed estrus response and duration of estrus was 66.66, 33.33, 33.33, 16.66 percent, and 23.8±6.2, 15.33±2.2, 16.3±0.8 and 13 hours in T1, T2, T3 and control groups respectively. The present study concluded that reproductive performance is higher in T1 and T3 compare to T2, and control. Hence foggers as microclimate alteration device was more advantageous compare to other.

Heat stress is a major problem causing economic losses to the dairy farmers. It causes hyperthermia and at its most severe form can lead to death. More commonly, heat stress reduces feed intake, milk yield, milk constituents, growth rate and reproductive function in livestock.It has a direct effect on breeding efficiency of female buffalo and reduces the intensity and duration of oestrus. Buffaloes fails to exhibit oestrus as a result of ovarian inactivity during summer. High environmental temperature causes hyper prolactinaemia, suppressing the secretion of gonadotrophins, which leads to an alteration in ovarian steroidogenesis. Heat stress also affects folliculogenesis, oocyte quality, Lactation length, calving interval, milk constituents and milk yield. Advances in management (i.e.,Cooling systems) have alleviated some of the negative impact of heat stress on buffaloes. In this review an attempt has been made to know the effect of heat stress and to discuss their impact on buffaloes.

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Objective/background: Collection of one spot and one morning sputum specimen is recommended for tuberculosis (TB) drug resistance surveys. This was a retrospective analysis of Mycobacterium tuberculosis cultures isolated from two spot sputum specimens collected from smear positive TB patients in a TB drug resistance survey. It was conducted to understand the value of a second specimen.Methods: A TB drug resistance survey was conducted in the state of Tamil Nadu, India, to estimate the prevalence of drug resistance among new sputum smear-positive (NSP) and previously treated (PT) patients diagnosed in Revised National Tuberculosis Control Program microscopy centers. A total of 2425 patients (1524 NSP and 901 PT cases) were enrolled in the study. From these patients, two spot sputum specimens (C and D) were collected within a period of 2 h. No preservative was added to sputum. The samples were transported at ambient conditions without cold storage to the central laboratory for culture of M. tuberculosis. Culture yield from each sample was computed and analyzed.Results: The proportion of cultures retrieved from C and D specimens among NSP cases (89.3% and 89.7%) and PT cases (90.8% and 90.3%) were similar. The culture grades of C and D samples were comparable (chi-square test, 3560.135; p<.001) and the agreement was moderate (kappa test, 0.454).Conclusion: The findings of the study reveal the adequacy of single spot sputum specimen from smear positive pulmonary TB patients for bacteriological examination in a quality-assured TB laboratory to determine precisely the level of drug resistance in a province of India.

Antifungal activity of 3-methylcarbazoles from Streptomyces sp. LJK109; an endophyte in Alpinia galangalThongchai Taechowisan, Srisakul Chanaphat, Wanwikar Ruensamran, Waya S. Phutdhawong

Mycobacteriophages produce lysins that break down the host cell wall at the end of lytic cycle to release their progenies. The ability to lyse mycobacterial cells makes the lysins significant. Mycobacteriophage Che12 is the first reported temperate phage capable of infecting and lysogenising Mycobacterium tuberculosis. Gp11 of Che12 was found to have Chitinase domain that serves as endolysin (lysin A) for Che12. Structure of gp11 was modeled and evaluated using Ramachandran plot in which 98 % of the residues are in the favored and allowed regions. Che12 lysin A was predicted to act on NAG-NAM-NAG molecules in the peptidoglycan of cell wall. The tautomers of NAG-NAM-NAG molecule were generated and docked with lysin A. The stability and binding affinity of lysin A – NAG-NAM-NAG tautomers were studied using molecular dynamics simulations.