Does "all disease begin in the gut"? The gut-organ cross talk in the microbiome.

The human microbiome, a diverse ecosystem of microorganisms within the body, plays pivotal roles in health and disease. This review explores site-specific microbiomes, their role in maintaining health, and strategies for their upkeep, focusing on oral, lung, vaginal, skin, and gut microbiota, and their systemic connections. Understanding the intricate relationships between these microbial communities is crucial for unraveling mechanisms underlying human health. Recent research highlights bidirectional communication between the gut and distant microbiome sites, influencing immune function, metabolism, and disease susceptibility. Alterations in one microbiome can impact others, emphasizing their interconnectedness and collective influence on human physiology. The therapeutic potential of gut microbiota in modulating distant microbiomes offers promising avenues for interventions targeting various disorders. Through interdisciplinary collaboration and technological advancements, we can harness the power of the microbiome to revolutionize healthcare, emphasizing microbiome-centric approaches to promote holistic well-being while identifying areas for future research.

An antimicrobial thiopeptide producing novel actinomycetes Streptomyces terrae sp. nov., isolated from subsurface soil of arable land.

An antimicrobial producing Gram-positive, aerobic, nonmotile, and filamentous actinobacterial strain SKN60T was isolated from soil The isolate exhibited 99.3% and 99.0% identity with Streptomyces laurentii ATCC 31255T and S. roseicoloratus TRM 44457T, respectively, in 16S rRNA gene sequence analysis. However, the genome sequence displayed maximum ANI (88.45%) and AAI (85.61%) with S. roseicoloratus TRM 44457T. Similarly, the dDDH showed 33.7% identity with S. roseicoloratus TRM 44457T. It formed a cluster with S. roseicoloratus TRM 44457T and S. laurentii ATCC 31255T in phylogenomic tree. Cell wall analysis revealed the presence of diphosphatidylglycerol, phosphatidylethanolamine, and phosphatidylcholine as major polar lipids and diaminopimelic acid as diagnostic diamino acid. Major fatty acids were iso-C15:0, anteiso-C15:0, and iso-C16:0. The G+C content was found to be 72.3 mol%. Genome sequence analysis using antiSMASH database showed occurrence of a thiopeptide biosynthesis gene cluster with 94% similarity to berninamycin from S. bernensis UC5144. The mass of 1146 Da is identical with berninamycin. But subtle differences observed in leader peptide sequence of thiopeptide and berninamycin. Notably, S. bernensis is not validly reported and thus SKN60T is the only strain containing berninamycin BGC as no other phylogenetic relative had it. Additionally, strain SKN60T differed in phenotypic and genetic characteristics with all phylogenetic relatives of the genus Streptomyces. Therefore, it is proposed as a novel species with the name Streptomyces terrae sp. nov. strain SKN60T (=MTCC 13163T; = JCM 35768T).

The Indigenous Volatile Inhibitor 2-Methyl-2-butene Impacts Biofilm Formation and Interspecies Interaction of the Pathogenic Mucorale Rhizopus arrhizus.

2-Methyl-2-butene has recently been reported to be a quorum-based volatile self-inhibitor of spore germination and growth in pathogenic Mucorale Rhizopus arrhizus. The present study aimed to elucidate if this compound can influence R. arrhizus biofilm formation and interspecies interaction. The compound was found to significantly decrease R. arrhizus biofilm formation (p < 0.001), with nearly 25% and 50% lesser biomass in the biofilms cultured with exposure to 4 and 32 µg/ml of 2-methyl-2-butene, respectively. The growth of pre-formed biofilms was also impacted, albeit to a lesser extent. Additionally, 2-methyl-2-butene was found to self-limit R. arrhizus growth during interspecies interaction with Staphylococcus aureus and was detected at a substantially greater concentration in the headspace of co-cultures (2338.75 µg/ml) compared with monocultures (69.52 µg/ml). Some of the C5 derivatives of this compound (3-methyl-1-butanol, 2-methyl-2-butanol, and 3-methyl-1-butyne) were also observed to partially mimic its action, such as inhibition of spore germination, but did not impact R. arrhizus biofilm formation. Finally, the treated R. arrhizus displayed changes in fungal morphology suggestive of cytoskeletal alterations, such as filopodia formation, blebs, increased longitudinal folds and/or corrugations, and finger-like and sheet-like surface protrusions, depending upon the concentration of the compound(s) and the planktonic or biofilm growth mode.

Volatile self-inhibitor of spore germination in pathogenic Mucorale Rhizopus arrhizus.

Rhizopus arrhizus is a common pathogenic Mucoralean mold that exists as a saprophyte, and is disseminated through sporangiospores, which germinate to form mycelia under suitable environmental or infection settings. Such morphological transitions are often mediated by self-produced effector molecules in a density-dependent fashion. This study aimed to elucidate if a quorum-dependent, cell-density-driven phenomenon exists in R. arrhizus, and identify the molecule(s) involved. The germination of R. arrhizus was observed to be reliant on the seeding density, with nearly 71% and 47% germination in Sabouraud dextrose and glucose asparagine media respectively at 1 × 105-1 × 106 spores/mL, and only 10% and 1% germination respectively with 1 × 108 spores/mL. The late-growth-stage supernatant also hindered the spore germination and liquid-culture biomass in a dose-dependent way. These effects were being mediated by a volatile inhibitor present in the headspace and supernatant of R. arrhizus cultures, identified as 2-methyl-2-butene by gas chromatography and electron ionization-quadrupole mass spectrometry. The compound was present in a density-dependent manner and considerably impaired fungal germ-tube emergence and elongation during germination. Spore swelling remained unaffected. Multiple thin protrusions comprising of F-actin and microtubules were seen emanating from the treated cells, suggestive of filopodia-like and cytoneme-like extensions. The same compound was also detected in Rhizomucor pusillus.

Facially Amphiphilic Cholic Acid-Lysine Conjugates as Promising Antimicrobials.

The emergence of multidrug-resistant microbes is a significant health concern posing a constant need for new antimicrobials. Membrane-targeting antibiotics are promising candidates with reduced ability of microbes to develop resistance. In the present investigation, the principal reason behind choosing cholic acid as the crucial scaffold lies in the fact that it has a facially amphiphilic nature, which provides ample opportunity to refine the amphiphilicity by linking the amino acid lysine. A total of 16 novel amphipathic cholic acid derivatives were synthesized by sequentially linking lysine to C3-ß-amino cholic acid methyl ester to maintain the hydrophobic/hydrophilic balance, which could be the essential requirement for the antimicrobial activity. Among the synthesized conjugates, a series with fluorenyl-9-methoxycarbonyl moiety attached to cholic acid via lysine linker showed promising antimicrobial activity against Staphylococcus aureus, Escherichia coli, and Candida albicans. A pronounced effect of increase in lysine residues was noted on the observed activity. The lead compounds were found to be active against drug-resistant bacterial and fungal clinical isolates and also improved the efficacy of antifungal agents amphotericin B and voriconazole. Membrane-permeability studies demonstrated the ability of these compounds to induce membrane damage in the tested microbes. The active conjugates did not show any hemolytic activity and were also found to be nontoxic to the normal cells as well as the examined cancer cell lines. The observed antimicrobial activity was attributed to the facial amphiphilic conformations, hydrophobic/hydrophilic balance, and the overall charge on the molecules.

Biofilm formation by Candida auris isolated from colonising sites and candidemia cases.

BACKGROUND: Candida auris, an emerging nosocomial pathogen, exhibits phenotypic variation. Non-aggregating C. auris isolates display greater biofilm-forming capacity and virulence than aggregate-forming isolates. Most of the studies till date have focused on clinical isolates. The biofilm-forming capacity of colonising isolates remains uninvestigated. OBJECTIVES: The present study aimed to elucidate the biofilm-forming capacity of the colonising isolates of C. auris, correlate it with their aggregation behaviour and antifungal susceptibility, and compare it with that of the isolates from blood-stream infection. METHODS: Colonising and clinical (candidemia) isolates of C. auris were screened for aggregation behaviour, biofilm-forming capacity and antifungal susceptibility testing. Aggregation behaviour was assessed microscopically. Biofilm-forming capacity was determined on 96-well flat-bottomed microtitre plates. Antifungal susceptibility testing was performed by broth microdilution assay. RESULTS: Aggregative and non-aggregative phenotypes were found to be predominantly associated with colonising and clinical isolates, respectively, with the former ones being stronger biofilm producers in the colonising group. Non-aggregative isolates in the colonising group showed lower susceptibility to amphotericin B and fluconazole than aggregative isolates. In contrast, no association was noted between biofilm formation, aggregation behaviour and antifungal susceptibility amongst the clinical isolates. CONCLUSION: Biofilm formation is a strain-dependent trait in C. auris, strongly associated with the type and phenotypic behaviour of the isolates. Colonising isolates of this fungus were found to be predominantly aggregative in nature, with a higher biofilm-forming capacity than non-aggregative ones.

Bile Acid Oligomers and Their Combination with Antibiotics To Combat Bacterial Infections.

The ever-growing risk of bacterial resistance is a critical concern. Among the various antimicrobial resistant bacterial strains, methicillin and vancomycin resistant Staphylococcus aureus are among the most dreadful, causing serious complications. On the basis of the hypothesis that microbes have reduced ability to develop resistance against membrane targeting antibiotics, bile acid oligomers having unique facially amphiphilic topologies were designed and synthesized. The oligomers with specific linkers exhibited potent and selective antibacterial activity against Gram-positive bacteria. The lead compounds also improved the efficacy of a range of known antibiotics belonging to different classes when tested in combination. The active dimers were found to be effective against antibiotic-resistant clinical isolates of S. aureus, including multidrug resistant isolates. A significant inhibitory activity against S. aureus biofilm, a highly drug-resistant bacterial phenotype often unresponsive to antibiotic therapy, was also noticed. No adverse effects were observed by these dimers in a cell viability assay against HEK293 cells.