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This study characterized the biosynthetic potential of the bacterium Achromobacter xylosoxidans strain ISP2-142-O-2-A associated with the sponge Haliclona sp. nov. Chemistry- and bioactivityguided purification of extracts from A. xylosoxidans afforded three compounds (1-3). The nucleoside 5'-deoxyadenosine (Compound 1) showed significant HIV cytoprotection activity with no cytotoxic activity to normal mammalian cells. The alkylquinolines 2-heptylquinolin-4-ol (Compound 2) and 2-nonylquinolin-4-ol (Compound 3) showed antimicrobial activity against Staphylococcus aureus and cytotoxicity to normal mammalian cells. This is the first report of Compounds 1-3 in A. xylosoxidans, and it is proposed that they have distinct roles for the bacterium to persist as a sponge-associated microorganism. Genomic analysis revealed the presence of 10 biosynthetic gene clusters (BGCs), indicating the potential of A. xylosoxidans strain ISP2-142-O-2-A as a source organism for other classes of bioactive natural products. [ABSTRACT FROM AUTHOR]

The Philippines has a high incidence of tuberculosis disease (TB), with an increasing prevalence of multidrug-resistant Mycobacterium tuberculosis (MDR-TB) strains making its control difficult. Although the M. tuberculosis "Manila" ancient lineage 1 strain-type is thought to be prevalent in the country, with evidence of export to others, little is known about the genetic diversity of circulating strains. By whole genome sequencing (WGS) 178 isolates from the Philippines National Drug Resistance Survey, we found the majority (143/178; 80.3%) belonged to the lineage 1 Manila clade, with the minority belonging to lineages 4 (European-American; n = 33) and 2 (East Asian; n = 2). A high proportion were found to be multidrug-resistant (34/178; 19.1%), established through highly concordant laboratory drug susceptibility testing and in silico prediction methods. Some MDR-TB isolates had near identical genomic variation, providing potential evidence of transmission. By placing the Philippine isolates within a phylogeny of global M. tuberculosis (n > 17,000), we established that they are genetically similar to those observed outside the country, including a clade of Manila-like strain-types in Thailand. An analysis of the phylogeny revealed a set of ~200 SNPs that are specific for the Manila strain-type, and a subset can be used within a molecular barcode. Sixty-eight mutations known to be associated with 10 anti-TB drug resistance were identified in the Philippine strains, and all have been observed in other populations. Whilst nine putative streptomycin resistance conferring markers in gid (8) and rrs (1) genes appear to be novel and with functional consequences. Overall, this study provides an important baseline characterisation of M. tuberculosis genetic diversity for the Philippines, and will fill a gap in global datasets and aid the development of a nation-wide database for epidemiological studies and clinical decision making. Further, by establishing a molecular barcode for detecting Manila strains it will assist with the design of diagnostic tools for disease control activities. [ABSTRACT FROM AUTHOR]