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OBJECTIVES:Thousands of cases of multidrug-resistant tuberculosis (TB) have been observed in the Philippines, but studies on the Mycobacterium tuberculosis (MTB) genotypes that underlie the observed drug resistance profiles are lacking. This study aimed to analyse the whole genomes of clinical MTB isolates representing various resistance profiles to identify single nucleotide polymorphisms (SNPs) in resistance-associated genes. METHODS:The genomes of ten MTB isolates cultured from banked sputum sources were sequenced. Bioinformatics analysis consisted of assembly, annotation and SNP identification in genes reported to be associated with resistance to isoniazid (INH), rifampicin (RIF), ethambutol (ETH), streptomycin, pyrazinamide (PZA) and fluoroquinolones (FQs). RESULTS:The draft assemblies covered an average of 97.08% of the expected genome size. Seven of the ten isolates belonged to the Indo-Oceanic lineage/EA12-Manila clade. Two isolates were classified into the Euro-American lineage, whilst the pre-XDR (pre-extensively drug-resistant) isolate was classified under the East Asian/Beijing clade. The SNPs katG Ser315Thr, rpoB Ser450Leu and embB Met306Val were found in INH- (4/7), RIF- (3/6) and ETH-resistant (2/6) isolates, respectively, but not in susceptible isolates. Mutations in the inhA promoter and in the pncA and gyrA genes known to be involved in resistance to INH, PZA and FQs, respectively, were also identified. CONCLUSIONS:This study represents the first effort to investigate the whole genomes of Philippine clinical strains of MTB exhibiting various multidrug resistance profiles. Whole-genome data can provide valuable insights to the mechanistic and epidemiological qualities of TB in a high-burden setting such as the Philippines.

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]