Pigmented Microbial Extract (PMB) from Exiguobacterium Species MB2 Strain (PMB1) and Bacillus subtilis Strain MB1 (PMB2) Inhibited Breast Cancer Cells Growth In Vivo and In Vitro.

Breast cancer (BC) continues to be one of the major causes of cancer deaths in women. Progress has been made in targeting hormone and growth factor receptor-positive BCs with clinical efficacy and success. However, little progress has been made to develop a clinically viable treatment for the triple-negative BC cases (TNBCs). The current study aims to identify potent agents that can target TNBCs. Extracts from microbial sources have been reported to contain pharmacological agents that can selectively inhibit cancer cell growth. We have screened and identified pigmented microbial extracts (PMBs) that can inhibit BC cell proliferation by targeting legumain (LGMN). LGMN is an oncogenic protein expressed not only in malignant cells but also in tumor microenvironment cells, including tumor-associated macrophages. An LGMN inhibition assay was performed, and microbial extracts were evaluated for in vitro anticancer activity in BC cell lines, angiogenesis assay with chick chorioallantoic membrane (CAM), and tumor xenograft models in Swiss albino mice. We have identified that PMB from the Exiguobacterium (PMB1), inhibits BC growth more potently than PMB2, from the Bacillus subtilis strain. The analysis of PMB1 by GC-MS showed the presence of a variety of fatty acids and fatty-acid derivatives, small molecule phenolics, and aldehydes. PMB1 inhibited the activity of oncogenic legumain in BC cells and induced cell cycle arrest and apoptosis. PMB1 reduced the angiogenesis and inhibited BC cell migration. In mice, intraperitoneal administration of PMB1 retarded the growth of xenografted Ehrlich ascites mammary tumors and mitigated the proliferation of tumor cells in the peritoneal cavity in vivo. In summary, our findings demonstrate the high antitumor potential of PMB1.

Biofilm-Associated Infections in Chronic Wounds and Their Management.

Chronic wounds including vascular ulcers, diabetic ulcers, pressure ulcers, and burn wounds show delayed progress through the healing process. Some of their common features are prolonged inflammation, persistent infection, and presence of biofilms resistant to antimicrobials and host immune response. Biofilm formation by opportunistic pathogens is a major problem in chronic wound management. Some of the commonly and traditionally used chronic wound management techniques are physical debridement and cleansing. In recent years, novel techniques based on anti-biofilm agents are explored to prevent biofilm-associated infections and facilitate wound healing. In this chapter, the role of biofilms formed by the ESKAPE pathogens (Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa) and Candida species in delayed wound healing have been discussed. The current and emerging techniques in the detection of biofilms for the management of wounds have been focused. The limitations of the existing therapeutics and novel wound management strategies have been deliberated.

Diketopiperazine derivative from marine actinomycetes Nocardiopsis sp. SCA30 with antimicrobial activity against MRSA.

Actinobacteria isolated from marine sources are a potential source of novel natural products. In this study, we report isolation, biological activity and characterization of secondary metabolites from strain Nocardiopsis sp. SCA30, isolated from marine sediments of Havelock Islands, Andaman and Nicobar, India. The ethyl acetate extracts of the isolate on screening for biological activity demonstrated antibacterial potency and antiproliferative activity. The extracts showed anticancer activity in a panel of cell lines, including HCT 15, HT 29, MCF 7 and MDA-MB 468, at concentrations ranging from 62.5 to 1000 µg/ml. A dose-dependent reduction in cell viability was observed in all the tested cell lines. The extract at 15 µg/ml and 30 µg/ml inhibited growth of methicillin-resistant Staphylococcus aureus ATCC NR-46071 and NR-46171 with MIC's of 15.62 and 7.81 µg/ml, respectively. LC-MS and NMR studies revealed that the antibacterial and anticancer compound isolated from Nocardiopsis sp. SCA30 is 1-acetyl-4-4(hydroxyphenyl)piperazine.

Coronavirus: occurrence, surveillance, and persistence in wastewater.

The coronavirus disease (COVID-19) outbreak reported in China in December 2019 has spread throughout the world. The WHO declared it as a pandemic in March 2020. The pandemic severely affected public health and the global economy. Many studies conducted on the coronavirus have helped us to elucidate its pathogenicity and pathophysiology. However, it is important to study the behavior of the pathogen in the environment to develop effective control measures. While studying the persistence and transmission of viruses in drinking water and wastewater systems, a low concentration of coronavirus and its nucleic acids have been detected in municipal wastewaters. This could be due to their high susceptibilities to degradation in aqueous environments. Epidemiological study on coronaviruses in wastewater will serve two purposes, i.e., in early detection of outbreak and in identifying asymptomatic carriers. In such cases, the epidemiological study will help in early detection of the presence of the virus in the community. Secondly, it will help in knowing if there are asymptomatic carriers, as such people do not show any signs of symptoms but shed the viruses in feces. The present review focuses on the epidemiological surveillance of wastewater for coronaviruses, as in recent years these are increasingly causing global pandemics. In this review we have discussed, the four pertinent areas of coronavirus study: (1) occurrence of coronavirus in wastewater, (2) wastewater based epidemiological surveillance of coronaviruses, (3) epidemiological surveillance tools used for detection of coronaviruses in sewage, and (4) persistence and sustainability of coronaviruses in wastewater.

Culturable diversity of bacterial endophytes associated with medicinal plants of the Western Ghats, India.

Bacterial endophytes are found in the internal tissues of plants and have intimate associations with their host. However, little is known about the diversity of medicinal plant endophytes (ME) or their capability to produce specialised metabolites that may contribute to therapeutic properties. We isolated 75 bacterial ME from 24 plant species of the Western Ghats, India. Molecular identification by 16S rRNA gene sequencing grouped MEs into 13 bacterial genera, with members of Gammaproteobacteria and Firmicutes being the most abundant. To improve taxonomic identification, 26 selected MEs were genome sequenced and average nucleotide identity (ANI) used to identify them to the species-level. This identified multiple species in the most common genus as Bacillus. Similarly, identity of the Enterobacterales was also distinguished within Enterobacter and Serratia by ANI and core-gene analysis. AntiSMASH identified non-ribosomal peptide synthase, lantipeptide and bacteriocin biosynthetic gene clusters (BGC) as the most common BGCs found in the ME genomes. A total of five of the ME isolates belonging to Bacillus, Serratia and Enterobacter showed antimicrobial activity against the plant pathogen Pectobacterium carotovorum. Using molecular and genomic approaches we have characterised a unique collection of endophytic bacteria from medicinal plants. Their genomes encode multiple specialised metabolite gene clusters and the collection can now be screened for novel bioactive and medicinal metabolites.

Anti-quorum sensing and biofilm inhibitory activity of Apium graveolens L. oleoresin.

Apium graveolens L. (Apiaceae) is a dietary herb used as a spice, condiment and medicine. A. graveolens (Celery) has been studied for its antimicrobial property and for its application as flavours in food industry. The present study investigated the Apium graveolens oleoresin as an anti-quorum sensing and antibiofilm agent. The quorum sensing and biofilm inhibition study was carried out using biosensor strains Chromobacterium violaceum CV12472 and Pseudomonas aeruginosa PAO1. The MIC of celery oleoresin against C. violaceum CV12472 and P. aeruginosa PAO1 was 10 and 25% v/v, respectively. Inhibition of violacein and biofilm formation was tested at concentrations of oleoresins ranging from 1.56 and 50% v/v. The oleoresins showed a concentration dependent QS inhibitory activity and at sub-MIC of 6.25 and 12.5% v/v, the oleoresins significantly inhibited violacein production and biofilm formation (p < 0.05). Similarly, the celery oleoresin had significant QS modulatory effect on swimming, swarming and twitching motility in P. aeruginosa PAO1 at 12.5% v/v (p < 0.05). The major phytoconstituents present in celery oleoresin as analysed by GC-MS were eicosadiene, benzenemethanol and methyl ester which have not been previously reported. The findings suggest that celery has QS and biofilm inhibitory potential against gram negative pathogens and can find application as food intervention techniques.

Inhibition of biofilm formation and quorum sensing mediated phenotypes by berberine in Pseudomonas aeruginosa and Salmonella typhimurium.

Quorum sensing is involved in biofilm formation and modulates virulence factor production in pathogenic bacteria. Quorum sensing inhibitors can be used as novel intervention strategies for attenuating bacterial pathogenicity. Berberine is an isoquinoline alkaloid with pharmacological properties. The present study investigated the sub-inhibitory concentrations of berberine for inhibiting biofilm formation and quorum sensing regulated phenotypes in the bacterial pathogens Pseudomonas aeruginosa PA01 and Salmonella enterica serovar Typhimurium. Berberine inhibited quorum sensing regulated violacein production in C. violaceum. It reduced the pigment production in the wild type strain at 1.6 mg mL-1 by 62.67%. In the opportunistic pathogen, P. aeruginosa PA01, at sub-MIC, it showed significant antibiofilm activity in by reducing biomass by 71.70% (p < 0.05). It prevented biofilm formation and inactivated biofilm maturation in bacterial pathogens at the concentration ranging from 0.019 to 1.25 mg mL-1. In silico studies showed that berberine interacted with the quorum sensing signal receptors, LasR and RhlR. Furthermore, its anti-infective properties in S. Typhimurium were studied. At sub-inhibitory concentrations of 0.019 mg mL-1, it reduced biofilm formation in S. Typhimurium by 31.20%. It significantly prevented invasion and adhesion of Salmonella invasion in the colonic cell, HT 29 by 55.37% and 54.68%, respectively. It was capable of reducing in vivo virulence in Caenorhabditis elegans infected with Salmonella at 0.038 mg mL-1 by 65.38%. Our results suggest that berberine, previously recognised for its antimicrobial activity, could find potential application as an anti-biofilm and anti-infective agent based on its quorum sensing inhibitory activity.

Endophytic Peptides - A Source of Therapeutic Agents.

Endophytic peptides have been considered as potential therapeutic sources of future antibiotics because of their broad-spectrum activities and different mechanisms of action compared to the conventional antibiotics. The world human population is increasingly facing different types of health issues. For instance, emerging wide array of the drug-resistant pathogens is a health concern. Research on bioactive agents and other natural products of microbes is essential to combat antimicrobial resistance. It is necessary to find new potential antibiotics to address this problem. The use of therapeutic plants in traditional medicine is well known. The medicinal plants contain endophytes which are repositories of bioactive compounds. The natural therapeutic agents produced by endophytes do have several potential applications in the field of pharmaceutical industry. Ecomycins, Pseudomycins, Munumbicins and Xiamycins are the antibacterial, antimycotic and antiplasmodial endophytic derived bioactive agents. Among these, some are having significant antiviral properties and inhibitory activity against plant and human bacterial pathogens. Therefore, to deal with emerging drug-resistant pathogens endophytic peptides could serve as a potential source of novel antibiotics. This review focuses on the peptides derived from plant endophytes, their biological and pharmaceutical applications, and their mechanisms of action.