Microbial Pathogenesis

For a pathogenic microbe to cause disease in a susceptible host, it must gain access to that host first. The pathogenicity of a microbe is determined by the virulence factors alongside other innate mechanisms. Apart from the initiation of infection, these virulence factors also enable the pathogenic microorganism to survive in the new environment within the susceptible host. They also enable the pathogenic microorganism to invade the host, colonize, and evade the host defense mechanisms. These virulence factors include; invasins, capsules, siderophores, adhesins, enzymes, endotoxins, and exotoxins. Key words: Pathogenicity factors and Pathological effect on cells.

Eco-Friendly, Green Approach for Synthesis of Bio-Active Novel 3-Aminoindazole Derivatives

In present chapter we have reported green and highly efficient method for synthesize novel series of substituted -1H-indazol-3-amine derivative (3a-h) by cyclocondensation reaction of substituted benzonitrile (1a-h) and substituted Hydrazine (2a-h) using ceric (IV) ammonium nitrate (CAN) as a catalyst, EtOH-H2O as a ecofriendly media and reaction was carried out under ultrasound irradiation green method. The structures of newly synthesized indazole derivative (3a-h) were corroborated through spectral investigation such as elemental analysis and spectral studies like IR, C13 NMR, Mass spectra and 1H NMR. The compounds were assessed for their in-vitro antimicrobial activity with pathogenic microbe comprising Gram positive bacterial strains, S. aureus and Gram negative strains E.coli, P.vulgaris, and S. typhi at different concentration. The consequence of bioassay is compared with standard drug Chloramphenicol.

Xylocarpus granatum Mangrove Fruit Extract and Sodium Alginate Extract Lotion as Potent Wound Treatment Medicine

A preliminary study to gauge the antimicrobial potency of Xylocarpus granatum mangrove fruit extract and sodium alginate extract against pathogenic microbe from the species Pseudomonas aeruginosa and Staphylococcus epidermidis. Lotions made of mangrove fruit extract (Sample 1) lotion and of a mixture of fruit extract and sodium alginate extract lotion (Sample 2) were topically tested on incision cut wound on mice abdominal area. The lotion was applied daily for five consecutive days. Observation on the test subjects were conducted to determine the rate of blood agglutination, tissue recovery rate, and fibroblast development rate using histology. The results showed that X. granatum extract lotion displayed significant antimicrobial activity against both pathogenic microbe species and did not show any conflict with the microbial activity found in sodium alginate lotion. Lotion adhesiveness test measured sample 1 at 0.26 seconds and sample two at 0.16 seconds. Both samples were shown to be oily in water. Subject observation showed blood coagulation on the first day, onset of tissue recovery on the second day and by the third day the wound had undergone complete tissue recovery. Observation on the fifth day showed that fibroblast tissue on the subject with sample 2 treatment was more solid than that with sample 1 treatment. It was concluded that the mix of X. granatum mangrove fruit and sodium alginate extracts showed most potency in wound treatment.Key words: X. granatum; incision wound; lotions; skin; histology; fibroblast.

Small Molecule Modulation of Microbiome Ecosystem: A Systems Pharmacology Perspective

An increasing body of evidence suggests that microbes are not only strongly associated with many human diseases but also responsible for the efficacy, resistance, and toxicity of drugs. Small-molecule drugs which can precisely fine-tune the microbial ecosystem on the basis of individual patients may revolutionize biomedicine. However, emerging endeavors in small-molecule microbiome drug discovery continue to follow a conventional “one-drug-one-target-one-disease” process. It is often insufficient and less successful in tackling complex systematic diseases. A systematic pharmacology approach that intervenes multiple interacting pathogenic species in the microbiome, could offer an attractive alternative solution. Advances in the Human Microbiome Project have provided numerous genomics data to study microbial interactions in the complex microbiome community. Integrating microbiome data with chemical genomics and other biological information enables us to delineate the landscape for the small molecule modulation of the human microbiome network. In this paper, we construct a disease-centric signed microbe-microbe interaction network using metabolite information of microbes and curated microbe effects on human health from published work. We develop a Signed Random Walk with Restart algorithm for the accurate prediction of pathogenic and commensal species. With a survey on the druggable and evolutionary space of microbe proteins, we find that 8-10% of them can be targeted by existing drugs or drug-like chemicals and that 25% of them have homologs to human proteins. We also demonstrate that drugs for diabetes are enriched in the potential inhibitors that target pathogenic microbe without affecting the commensal microbe, thus can be repurposed to modulate the microbiome ecosystem. We further show that periplasmic and cellular outer membrane proteins are overrepresented in the potential drug targets set in pathogenic microbe, but not in the commensal microbe. The systematic studies of polypharmacological landscape of the microbiome network may open a new avenue for the small-molecule drug discovery of microbiome.Author SummaryAs one of the most abundant components in human bodies, the microbiome has an extensive impact on human health. Pathogenic-microbes have become emerging potential therapeutic targets. Small-molecule drugs that only intervene in the growth of a specific pathogenic microbe without considering the interacting dynamics of the microbiome community may disrupt the ecosystem homeostasis, thus can cause drug side effect or prompt drug resistance. To discover novel drugs for safe and effective microbe-targeting therapeutics, a systematic approach is needed to fine-tune the microbiome ecosystem. To this end, we built a disease-centric signed microbe-microbe interaction network which accurately predicts the pathogenic or commensal effect of microbe on human health. Based on annotated and predicted pathogens and commensal species, we performed a systematic survey on therapeutic space and target landscape of existing drugs for modulating the microbiome ecosystem. Enrichment analysis on potential microbe-targeting drugs shows that drugs for diabetes could be repurposed to maintain the healthy state of microbiome. Furthermore, periplasmic and cellular outer membrane proteins are overrepresented in the potential drug targets of pathogenic-microbes, but not in proteins that perturb commensal-microbes. Our study may open a new avenue for the small molecule drug discovery of microbiome.

Riding the Shi: From Infection Barriers to the Microbial City

How can a microbial approach to global health security protect life? Contemporary infection control mechanisms set the human and the pathogenic microbe against each other, as the victim versus the menace. This biomedical polarization persistently runs through the contemporary dominant mode of thinking about public health and infectious disease governance. Taking its cue from the currently accepted germ theory of disease, such mechanisms render a global city like Hong Kong not only pervasively “on alert” and under threat of unpredictable and pathogenic viruses and other microbes, it also gives rise to a hygiene and antimicrobial politics that is never entirely able to control pathogenic circulation. The article draws on recent advances in medical microbiology, which depart from germ theory, to invoke an ecological understanding of the human-microbe relation. Here, while a small number of viruses are pathogenic, the majority are benign; some are even essential to human life. Disease is not just the outcome of a pathogenic microbe infecting a human host but emerges from socioeconomic relations, which exacerbate human-animal-microbial interactions. In a final step, the article draws on Daoist thought to reflect on the ways that such a microbial understanding translates into life and city dwelling.

Rapid and extensive karyotype diversification in haploid clinical Candida auris isolates

Candida auris is a newly emerging pathogenic microbe, having been identified as a medically relevant fungus as recently as 2009. It is the most drug-resistant yeast species known to date and its emergence and population structure are unusual. Because of its recent emergence we are largely ignorant about fundamental aspects of its general biology, life cycle, and population dynamics. Here we report the karyotype variability of 26 C. auris strains representing the four main clades. We demonstrate that all strains are haploid and have a highly plastic karyotype containing five to seven chromosomes, which can undergo marked alterations within a short time-frame when the fungus is put under genotoxic, heat, or osmotic stress. No simple correlation was found between karyotype pattern, drug resistance, and clade affiliation indicating that karyotype heterogeneity is rapidly evolving. As with other Candida species, these marked karyotype differences between isolates are likely to have an important impact on pathogenic traits of C. auris.

‘YELLOW SYNDROME’ IN SCLERACTINIAN CORALS THROUGHOUT BINTAN DISTRICT, KEPULAUAN RIAU PROVINCE, INDONESIA

Coral disease surveys were conducted in Bintan, Kepulauan Riau Province. The purpose was to identify the abundance of corals showing signs of Yellow Syndrome (YS) disease and to describe similar pathological signs to that of AYBD throughout Bintan District. Three belt transects (2 m x 50 m in size) were set up to determine the abundance of coral reef attacked by YS disease. Line intercept transects were used to determine the percentage of live corals in the surveyed areas. The survey showed that the YS disease syndrome attacked 8 different genera i.e. Acropora, Montipora, Porites, Pavona, Turbinaria, Favia, Platygyra, and Favites. The highest attack happened at Mapur Island (0.06 kol/m2) on Porites lutea, Turbinaria peltata, T. mesenterina, Acropora bruggemanni, and Pavona frondifera. The survey also indicated that there may have been at least two types of YS i.e. the first type caused by a boring and/or over-growing sponge species and the second type caused by a kind of pathogenic microbe. Regardless the causal agent of YS, the severity of YS attack on coral urged immediate action to be undertaken and should include initial microscopic and histology examinations. Based on this initial microscopic and histology examinations it was found out that YS bears a close resemblance to the Arabian Yellow Band Disease. This study, however, argued that the word “disease” may have been incorrectly used without identifying a specific causal agent.

Biomembrane mimics and their roles in anti-bacterial drug discovery

Cell membrane is at the frontline of the battle between pathogenic microbe and host. A thorough understanding of bacterial membrane is fundamental to tackle infection disease. Membrane mimetic provides a powerful tool for mechanistic interrogation of drug-membrane interaction. Herein, we summarized major features of bacterial and mammalian cell in context of antibacterial therapy. Much details were given to model membranes and their application in mechanistic studies. Current challenge in antibacterial therapy and perspective of membrane mimics in antibacterial drug discovery were also provided.