Evolution and transmission of antibiotic resistance is driven by Beijing lineage Mycobacterium tuberculosis in Vietnam

A previous investigation has elucidated the landscape of Mtb genomic diversity and transmission dynamics in Ho Chi Minh City, Vietnam. Here, we expand the scope of this survey by adding a substantial number of additional genomes (total sample size: 2,542) and phenotypic drug susceptibility data for the majority of isolates. We aim to explore the prevalence and evolutionary dynamics of drug resistance and our ability to predict drug resistance from sequencing data. Among isolates tested phenotypically against first-line drugs, we observed high rates of streptomycin [STR, 37.7% ( N = 573/1,520)] and isoniazid resistance [INH, 25.7% ( N = 459/1,786)] and lower rates of resistance to rifampicin [RIF, 4.9% ( N = 87/1,786)] and ethambutol [EMB, 4.2% ( N = 75/1,785)]. Relative to global benchmarks, resistance to STR and INH was predicted accurately when applying the TB-Profiler algorithm to whole genome sequencing data (sensitivities of 0.81 and 0.87, respectively), while resistance to RIF and EMB was predicted relatively poorly (sensitivities of 0.70 and 0.44, respectively). Exploring the evolution of drug resistance revealed the main phylogenetic lineages to display differing dynamics and tendencies to evolve resistance via mutations in certain genes. The Beijing sublineage L2.2.1 was found to acquire de novo resistance mutations more frequently than isolates from other lineages and to suffer no apparent fitness cost acting to impede the transmission of resistance. Mutations conferring resistance to INH and STR arose earlier, on average, than those conferring resistance to RIF and are now more widespread across the phylogeny. The high prevalence of “background” INH resistance, combined with high rates of RIF mono-resistance (20.7%, N = 18/87), suggests that rapid assays for INH resistance will be valuable in this setting. These tests will allow the detection of INH mono-resistance and will allow multi-drug-resistant isolates to be distinguished from isolates with RIF mono-resistance. IMPORTANCE Drug-resistant tuberculosis (TB) infection is a growing and potent concern, and combating it will be necessary to achieve the WHO’s goal of a 95% reduction in TB deaths by 2035. While prior studies have explored the evolution and spread of drug resistance, we still lack a clear understanding of the fitness costs (if any) imposed by resistance-conferring mutations and the role that Mtb genetic lineage plays in determining the likelihood of resistance evolution. This study offers insight into these questions by assessing the dynamics of resistance evolution in a high-burden Southeast Asian setting with a diverse lineage composition. It demonstrates that there are clear lineage-specific differences in the dynamics of resistance acquisition and transmission and shows that different lineages evolve resistance via characteristic mutational pathways

KOG functional classification.

<p>KOG functional classification.</p

Nine strongly cold-responsive genes found in all five tissues at both 13°C and 5°C.

<p>Nine strongly cold-responsive genes found in all five tissues at both 13°C and 5°C.</p

Transcriptome Analysis to Identify Cold-Responsive Genes in Amur Carp (<i>Cyprinus carpio haematopterus</i>)

<div><p>The adaptation of fish to low temperatures is the result of long-term evolution. Amur carp (<i>Cyprinus carpio haematopterus</i>) survives low temperatures (0-4°C) for six months per year. Therefore, we chose this fish as a model organism to study the mechanisms of cold-adaptive responses using high-throughput sequencing technology. This system provided an excellent model for exploring the relationship between evolutionary genomic changes and environmental adaptations. The Amur carp transcriptome was sequenced using the Illumina platform and was assembled into 163,121 cDNA contigs, with an average read length of 594 bp and an N50 length of 913 bp. A total of 162,339 coding sequences (CDSs) were identified and of 32,730 unique CDSs were annotated. Gene Ontology (GO), EuKaryotic Orthologous Groups (KOG) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to classify all CDSs into different functional categories. A large number of cold-responsive genes were detected in different tissues at different temperatures. A total of 9,427 microsatellites were identified and classified, with 1952 identifying in cold-responsive genes. Based on GO enrichment analysis of the cold-induced genes, “protein localization” and “protein transport” were the most highly represented biological processes. “Circadian rhythm,” “protein processing in endoplasmic reticulum,” “endocytosis,” “insulin signaling pathway,” and “lysosome” were the most highly enriched pathways for the genes induced by cold stress. Our data greatly contribute to the common carp (<i>C</i>. <i>carpio</i>) transcriptome resource, and the identification of cold-responsive genes in different tissues at different temperatures will aid in deciphering the genetic basis of ecological and environmental adaptations in this species. Based on our results, the Amur carp has evolved special strategies to survive low temperatures, and these strategies include the system-wide or tissue-specific induction of gene expression during their six-month overwintering period.</p></div

Global gene expression profiles of Amur carp.

<p>Global gene expression profiles of Amur carp.</p

The top 30 most abundant GO sub-categories.

<p>The top 30 most abundant GO sub-categories.</p

Gene ontology (GO) enrichment analysis of cold-responsive genes.

<p>Gene ontology (GO) enrichment analysis of cold-responsive genes.</p

KEGG classification.

<p>KEGG classification.</p

Point-and-Shoot Strategy for Identification of Alcoholic Beverages

The lack of point-and-shoot detection methods of alcoholic beverages (ABs) available for ordinary people is a common cause of the overflow of various counterfeit ABs. Here, we, for the first time, provide a point-and-shoot identification for ABs via a smartphone. Using density functional theory, we find the binding ability of an ethylenediamine-functionalized polydiacetylene (P4) can reach a desirable trade-off among organic molecules in ABs. We therefore construct a versatile array consisting of P4 with different concentrations, which is able to generate unique color response patterns toward different ABs. The color response patterns are further analyzed by a custom-designed image processing algorithm based on machine learning. Finally, the identification of ABs can be achieved by capturing and analyzing the color pattern using an imaging recognition programmer on a smartphone, and the entire process is as fast as quick response (QR) code scanning. Our point-and-shoot strategy makes the identification of ABs accessible to every mobile phone user