Infection Genetics and Evolution最新文献

Mycobacterium avium complex (MAC) is an emerging pathogen leading to public health concerns in developing and developed countries, particularly among immunocompromised individuals and patients with structural lung diseases. Current clinical guidelines recommend combination antibiotic therapy for treating MAC pulmonary disease (MAC-PD). However, the rising prevalence of antibiotic resistance poses significant challenges, including treatment failure and clinical recurrence. A deeper understanding of the mechanisms underlying MAC antibiotic resistance is essential to improve treatment outcomes. This study investigates the genetic variations associated with aminoglycoside resistance in an antibiotic-induced Mycobacterium intracellulare mutant derived from a clinical strain. Whole-genome analysis identified seven mutations in the aminoglycoside-resistant mutant, including single nucleotide polymorphisms (SNPs) and insertions/deletions (InDels). Key genetic alterations included a frameshift variant in a gene encoding a secreted protein antigen, missense mutations in rpsL and rsmG, and synonymous and in-frame deletion variants in srfAB and mtrB, respectively. These findings highlight the complex genetic landscape of aminoglycoside resistance in M. intracellulare. Understanding these resistance determinants provides valuable insights for developing diagnostic tools to detect drug-resistant MAC strains and optimizing therapeutic strategies for managing MAC infections in clinical practice.

Infectious bronchitis (IB), caused by the infectious bronchitis virus (IBV), is a highly contagious chicken disease, causing economic losses worldwide. New IBV strains and variants continue to emerge despite using inactivated and live-attenuated vaccines to prevent or control IB. In this study, the S1 genes of 46 IBV strains, isolated from commercial chicken flocks between 2003 and 2024 in Korea were sequenced and genetically characterized. The IBV isolates belonged to Korean group II (K-II), which was included in the GI-19 lineage. The K-II was divided into five sub-genogroups (a-e) based on phylogenetic tree analysis results and nucleotide identification of the S1 gene. Of these, K-IId was the most common genotype in Korea; however, eight novel isolates belonging to the K-IIe sub-genotype were discovered. The nucleotide and amino acid identities of the other four K-II sub-genotypes and the eight isolates were 84.42-95.89 % and 84.02-95.86 %, respectively. The complete genomes of the eight K-IIe isolates were obtained using next-generation sequencing. Various recombination patterns were observed despite the high homology of the S1 gene among the eight IBV strains. Among the eight K-IIe isolates, six were recombinants, exhibiting recombinations between K-IIe and K-IIc, K-IIe and K-IIa, and with the live vaccine strain. Most recombination breakpoints were detected in the nsp2 region of the ORF1a, S2, and M genes. The present study proposed new classification criteria for the K-II belonged to the GI-19 lineage prevalent in South Korea and revealed the recombination patterns of recently identified novel isolates, providing important information on novel viral sub-genotype strains and IBV evolution.

Paragonimiasis, caused by infection with lung flukes of the genus Paragonimus, remains a significant public health concern in Southeast Asia. In Lao People's Democratic Republic (Lao PDR), information on the distribution and genetic diversity of Paragonimus species is limited. This study investigated Paragonimus metacercariae in freshwater (mountain) crabs and analyzed their genetic diversity and phylogenetic relationships. Thirty-six crabs (Indochinamon sp.) were received from Xiang Ngeun and Pak Ou in Luang Prabang Province, northern Lao PDR. Partial mitochondrial 16S rRNA sequences obtained from four crabs indicated a moderately close relationship with Indochinamon ou. A total of 81 metacercariae identified morphologically as Paragonimus heterotremus were found among 13 out of the 32 crabs dissected (40.6 %). Molecular analyses targeting the ribosomal ITS2 region and mitochondrial cytochrome c oxidase subunit 1 (cox1) gene were conducted on these metacercariae. Phylogenetic analyses revealed that P. heterotremus sequences from Lao PDR clustered with those from neighboring countries-China, Myanmar, Vietnam and Thailand-suggesting potential genetic connectivity among eastern Asian populations. Haplotype-network analysis demonstrated significant genetic diversity within P. heterotremus populations from Lao PDR, separating into two distinct haplotype groups, one of which was unique to this study. This is the first report that Indochinamon sp. crabs serve as key intermediate host for a member of the P. heterotremus complex in Luang Prabang Province and highlights the parasite's genetic diversity in this region.

Wild carnivorans are key hosts of parvoviruses of relevance for animal health and wildlife conservation. However, the distribution and diversity of parvoviruses among wild carnivorans are under-investigated, particularly in Southern Europe. We evaluated the presence, spread, and diversity of multi-host protoparvoviruses (canine parvovirus type 2 (CPV-2), feline panleukopenia virus (FPV)), and amdoparvoviruses in 12 carnivoran species from Northern Spain to explore viral ecology. Broad-range PCRs were used to screen spleens (N = 157) and intestines (N = 116) from 171 road-killed mustelids, viverrids, and felids; identified viruses were molecularly characterized. We detected an Asian-like CPV-2c strain in the spleen of one wildcat (Felis silvestris, 1/40, 2.5 %), a globally distributed FPV strain in the spleen of one Eurasian badger (Meles meles, 1/35, 2.9 %), a novel amdoparvovirus (European mustelid amdoparvovirus 1), in the intestine and spleen of one stone marten (Martes foina, 1/16, 6.3 %) and in the spleen of one Eurasian badger (1/35, 2.9 %), the red fox fecal amdovirus (RFFAV) in the intestine and spleen of three wildcats (3/40, 7.5 %), and a novel amdoparvovirus closely related to RFFAV (European felid amdoparvovirus 1) in one wildcat (1/40, 2.5 %). We observed a correlation between the phylogeny of carnivorans and the one of amdoparvoviruses, possibly indicating virus-host co-evolution. Species originating from North America and Eurasia formed different clades, indicating local segregation in the absence of man-linked transboundary movements. In contrast, CPV-2 and FPV strains were internationally dispersed. Different parvovirus species co-occur in sympatric host populations, and higher viral diversity and additional hosts will likely be identified in future studies.

Whole genome sequencing has been used to investigate the genomic diversity of M. tuberculosis in the northern and southern states of India, but information about the eastern part of the country is still limited. Through a sequencing-based strategy, this study seeks to comprehend the diversity and drug resistance pattern in the eastern region. A total of 102 M. tuberculosis isolates from North East (n = 54), and Odisha (n = 48) were sequenced along with 7 follow up isolates from Sikkim. The pre-XDR and XDR isolates diagnosed as per the NTEP diagnostic algorithm were subjected for phenotypic second-line liquid culture drug susceptibility testing in MGIT-960 system. After filtering out low quality isolates based on taxonomic classification and depth of coverage, variant calling was performed. We observed a high prevalence of multi-drug resistant TB (MDR-TB) lineage 2 (52/54) isolates in northeast whereas there was a mixed representation of lineage 1 (30/48) & lineage 3 (11/48) in Odisha. The MDR-TB isolates from Sikkim posed a high rate (51/53) of fluoroquinolone resistance and pairwise SNV distances (≤10) indicating possible local transmission events in the region. We observed occurrence of genetic variations in genes associated with bedaquiline and delamanid resistance. Our findings show the diversity of M. tuberculosis vary across the eastern regions, in north eastern states lineage 2 has a dominant presence while lineage 1 and 3 has mixed representation in Odisha. The high prevalence of fluoroquinolone resistance in north eastern region associated with variations in gyrA gene and may have been caused by local transmission events based on genomic similarities.

The growing issue of drug resistance, particularly multidrug-resistant TB (MDR-TB), has exacerbated this problem. The rise of drug resistance TB is a severe global health concern. In Thailand, a persistent community outbreak of primary MDR-TB has been confirmed in the Tha Maka district of Kanchanaburi province, with an increasing prevalence of MDR-TB among newly diagnosed pulmonary tuberculosis cases. It was the first site in Thailand where a cluster of MDR-TB, caused by the Asian African 3 Modern Beijing strain, and XDR-TB, caused by L2.1, outbreaks were reported. This study aims to assess the MDR-TB outbreak in detail by characterizing the genomic profiles of the prevalent MDR-TB strains and examining their geographical distribution within the affected district. Through whole-genome sequencing (WGS) and bioinformatic analysis of 188 MTB isolates, the study identified three major phylogenetic lineages: the East Asian lineage (L2, 92 %), the Indo-Oceanic lineage (L1, 5.9 %), and the Euro-American lineage (L4, 2.1 %). The detailed sub-lineage distribution offers valuable insights into the predominant genetic clusters of M. tuberculosis within the sampled population. Notably, Lineage 2, specifically the L2.2.M3 sub-lineage, stood out as the dominant strain of MDR-TB, accounting for 77.7 % of the isolates. This finding underscores the significant prevalence of the L2.2.M3 sub-lineage and its potential role in the local transmission dynamics of tuberculosis. The high proportion and genetic homogeneity of the L2.2.M3 cluster among MDR-TB patients may indicate the strain's adaptation for more effective transmission within the Thai population. The increasing prevalence of this pathogenic strain could significantly impact tuberculosis control programs. Early diagnosis and contact tracing with chemotherapeutic preventive therapy for MDR-TB will be essential in inhibiting the spread and reactivation of these strains. Additionally, further studies are needed to prospectively identify transmission routes through contact tracing and real-time genotypic methods. It will also be crucial to ensure that future vaccines and/or recommended chemoprophylaxis therapy for MDR-TB will provide protection against these emerging strains.

Infections with the liver fluke (Fasciola hepatica) cause economic losses in cattle production worldwide. Also, infections with rumen flukes (Calicophoron/Paramphistomum spp.) are gaining importance in grazing cattle in Europe. However, increasing resistance of helminth parasites against anthelmintics and limitations in treatment emphasize the need for alternative breeding approaches. This study included 1602 dairy cows kept on 29 farms with 2423 observations for F. hepatica and Calicophoron/Paramphistomum spp. egg counts per gram faeces (EPG). The EPGs were binary defined (infected: EPG > 0; non-infected: EPG = 0) and logarithmically transformed. The pedigree included 7939 cows. Genotypes (777 k) were available for 214 cows. A single-step GBLUP (ssGBLUP) model was applied to estimate genetic parameters for infection traits. Genomic breeding values from ssGBLUP were used in a single-step genome-wide association study (ssGWAS) to identify genetic variants associated with helminth infections. The heritability for liver fluke infections was up to 0.09, and up to 0.34 for rumen fluke infections. The genetic correlations between liver and rumen fluke infections ranged from 0.49 to 0.53, indicating that breeding for improved resilience to both helminth taxa is possible simultaneously. The ssGWAS revealed four SNPs for liver fluke infections on BTA 5, 13, 26 and 29, and 17 SNPs for rumen fluke infections on BTA 3 and 23. The SNPs for liver fluke infections were annotated to 12 potential candidate genes, most of which involved in liver fibrosis and immunity. The LRRC8B gene was found to be involved in host-rumen fluke interactions.

Hepatitis C still poses a threat to public safety, and there are few reports of hepatitis C virus (HCV) in Heilongjiang Province. Therefore, we aimed to study the epidemiology and resistance-associated substitutions (RASs) of HCV in Heilongjiang and explore the efficacy of treatment. 7019 specimens from Heilongjiang Province were subjected to the genotype identification. The Autoregressive Integrated Moving Average (ARIMA) model was utilized to predict HCV infection trends from 2024 to 2030. The Sanger sequencing was performed on samples of genotype(GT) 1b and 2a to investigate RASs. Phylogenetic analysis was conducted to assess the similarity of local HCV sequences with those from other countries. In addition, we tracked the effect of patients treated with DAAs and the relationship between efficacy and RASs. The predominant HCV subtypes in Heilongjiang were 1b (47.51 %) and 2a (43.85 %). From 2012 to 2023, the proportions of GT2a, GT3a, GT3b, and GT6a gradually increased. And the prevalence of GT2a will exceed that of GT1b over the next seven years. The proportion of RASs in GT1b and GT2a NS5A region was 73.47 % and 15.22 %, respectively. And the proportion of RASs in GT1b NS5B region was 100 %. Local HCV sequences exhibited phylogenetic relationships with sequences from other countries. The GT1b R30Q and GT2a C92S were correlated with drug efficacy. K107R and P206S, which have not been reported in the literature, were also related to drug efficacy. The epidemiology of HCV genotypes in Heilongjiang is becoming increasingly diverse. HCV GT1b has a large variety and a high proportion of RASs, and patients infected with this genotype of HCV need to be sequenced before treatment.

Background: The goal is to identify methylation sites linked to transmission and their impact on host gene expression and HBV spread, aiming to uncover new molecular targets for preventing and treating intrauterine HBV infection.

Methods: This study recruited 1205 infants born to HBsAg-positive mothers in Liuzhou City, China, between July 2023 and January 2024. Infants were followed up at 7-12 months of age and classified as HBsAg-positive (case, n = 5) or HBsAg-negative (control, n = 14) based on serological testing. Peripheral blood samples were collected for DNA extraction. DNA methylation profiling was performed using the Illumina Infinium MethylationEPIC BeadChip (850 K). Data were processed using the ChAMP package in R, including quality control, normalization, and identification of Differentially Methylated Positions (DMPs) and differentially methylated regions (DMRs). DMPs and DMRs were annotated using ANNOVAR 2018Apr16, and GO enrichment analysis was conducted using DAVID. The study was approved by the Guangxi University of Chinese Medicine Ethics Committee, and informed consent was obtained.

Results: We identified 734,978 DMPs and 660 DMRs, with 1813 DMPs and 221 DMRs showing significant differences between groups. HBV-infected infants exhibited lower overall genomic methylation levels, with significant concentrations in gene body regions and CpG islands. GO enrichment analysis indicated that differentially methylated genes were enriched in processes related to cell adhesion and calcium ion binding.

Conclusions: Prenatal HBV exposure was associated with significant infant hypomethylation, particularly in regulatory regions like TSS1500, TSS200, and CpG islands, potentially impacting gene expression. Enrichment of immune-related pathways among differentially methylated genes suggests that HBV may alter infant immune development through epigenetic modifications.