Infection Genetics and Evolution最新文献

Melioidosis is a zoonotic disease, with its outbreaks being rare and indicative of an unusual concurrence of extreme climate and natural environmental factors. An outbreak of melioidosis cases emerged in Hainan following Typhoon “Dianmu” from October to December 2021, presenting an opportunity to identify the environmental sources of infection for these cases due to its nature as a well-defined point-source cluster. To investigate the relationship between the occurrence of these melioidosis cases and the environment, we extracted the entire genome of 25 clinical strains and conducted MLST typing, followed by whole genome sequencing and analysis of molecular genetic information for four ST46 genotypes from these strains. Phylogenetic and evolutionary relationships between Hainan sequence types (STs) and those found in other endemic regions were analyzed using IslandPath-DIMO, PHASTER, e-BURST, PHYLOViZ, and the maximum likelihood method. Notably, a total of 25 clinical strains were identified, encompassing 12 STs (ST46, ST1105, ST1991, ST30, ST1992, ST50, ST164, ST55, ST70, ST1993, ST1545, and ST58), with ST1991, ST1992, and ST1993 being newly discovered subtypes. PHYLOViZ clustering analysis divided the strains into two groups (A and B), both closely related to the Asian region. Phylogenetic tree analysis further revealed that most of the strains in this study were closely related to those found in Australia and Thailand. Analysis of patient information and visits to their residences suggested that contaminated water sources might be the primary source of infection during this outbreak.

Our findings underscore that extreme weather events, such as typhoons, significantly increase the infection rate of B. pseudomallei, along with its genetic diversity, necessitating additional prevention strategies to control these B. pseudomallei infections.

Objective

In Guangdong Province, hepatitis C virus (HCV) had been found to confer resistance to direct-acting antivirals (DAAs). There were few studies of HCV subtypes and resistance-associated substitutions (RASs) of HCV in different high-risk populations. In this study, we aimed to determine the subtype distribution and the RASs in high-risk population groups, including drug users (DU), men who have sex with men (MSM), female sex workers (FSW), and male patients with sexually transmitted diseases (STD) in Guangdong Province (a highly developed province with a large population).

Methods

Using a city-based sampling strategy,1356 samples were obtained from different population groups. Phylogenetic analyses determined subtypes based on Core, NS5B, or NS5A sequences. HCV subtype distribution and RASs in various risk groups and regions were analyzed.

Results

Ten subtypes, of which 6 h and 6 k were novel in Guangdong, were identified. The primary subtype among all risk groups was 6a. RASs in 1b and 3a were different from those observed in other studies. Subtype 3b in western Guangdong was higher than the other three regions. No RASs were found in 6a or any other genotype 6.

Conclusions

The HCV subtypes are expanding in high-risk populations in Guangdong. Drug use by other risk groups and commercial sex by DU may bridge the dissemination of 6a from DU to other populations. The RAS profiles of 1b and 3a differed from those reported in studies conducted in southwestern China. Further research is required to determine the reason for this discrepancy. Moreover, the combination of RASs was high in subtype 3b. To guide HCV treatment of subtype 3b, pretreatment subtyping of HCV genotype 3 should be considered in western cities in the near future.

Purpose

We aimed to characterise Yersinia enterocolitica from human clinical specimens in Switzerland using epidemiological, microbiological and whole-genome sequencing (WGS) data.

Methods

Isolates (n = 149) were collected between January 2019 and December 2023. Epidemiological data was noted and strains were characterized by biochemical and serological typing, antimicrobial susceptibility testing (AST), and WGS-based analysis.

Results

Most of the isolates (86%) were from stool specimens and 52% were from male patients. The patients' median age was 28 years (range < 1–94 years). Typing assigned the isolates to bioserotype 4/O:3 (44%), biotype 1A (34%), bioserotype 2/O:9 (21%), and bioserotype 3/O:3 (1%). WGS identified Y. enterocolitica (n = 147), Y. alsatica (n = 1) and Y. proxima (n = 1). Seven isolates were multidrug resistant (MDR) and harboured plasmid pAB829 carrying aph(3″)-Ib, aph(6)-Id, and tet(Y) (n = 1), pAC120 carrying aph(6)-Id and tet(A) (n = 2), or a 12.6 kb Tn2670-like transposon containing catA1, aadA12, sul1, and qacEΔ1 (n = 4). Virulence factors (VFs) included ail (n = 99), invB, (n = 145), ystA (n = 99), ystB (n = 48) and pYV-associated VFs (n = 93). MLST and cgMLST analysis showed that BT 1A strains consisted of several STs and were highly diverse, whereas BT 2/O:9 strains were all ST12 and clustered closely, and BT 4/O:3 strains mostly belonged to ST18 but were more diverse. SNP analysis revealed two highly clonal BT 4/O:3 subpopulations with wide spatio-temporal distribution.

Conclusions

Y. enterocolitica BT 1A, BT 2/O:9 and BT 4/O:3 are frequently associated with human yersiniosis in Switzerland. WGS-based subtyping of Y. enterocolitica is a powerful tool to explore the genetic diversity and the pathogenic potential of human isolates.

Despite intensive control efforts, Foot and mouth disease (FMD) outbreaks continue to occur regularly in Egypt and resulting in dramatic economic losses to the livestock industry. During 2018 and 2022, FMD was clinically suspected among previously vaccinated cattle in Beheira and Kafr El-Sheikh provinces, Egypt. FMDV RNA was detected in 18 (45%) out of 40 epithelial tissue samples using real-time RT-PCR based on a pan-FMDV primers set. The 2018 outbreak isolates (n = 8) included the FMDV serotypes A and SAT2, whereas all isolates (n = 10) from the 2022 outbreak belonged to the FMDV serotype A. Four selected isolates, designated FMDV/SAT2/EGY/Beheira/2018, FMDV/A/EGY/Kafr El-Sheikh/2018, FMDV/A/EGY/Kafr El-Sheikh/2022 and FMDV/A/EGY/Behiera/2022, were characterized on the basis of partial VP1 gene sequence analysis. The FMDV/SAT2/EGY/Beheira/2018 strain was clustered within the Lib-12 lineage of the topotype VII and shared 79.2–98.4% nucleotide identity with other Egyptian SAT2 strains available in Genbank database. On the other hand, the three FMDV serotype A sequences shared 74.4–99.1% nucleotide identity with each other. Also, they were phylogenetically classified within two distinct topotypes. The FMDV/A/Egy/Kafr El-Sheikh/2018 strain was grouped within the Asian topotype, meanwhile the FMDV/A/EGY/Kafr El-Sheikh/2022 and FMDV/A/EGY/Behiera/2022 strains were grouped together within the genotype IV of the African topotype. Interestingly, the deduced amino acid sequences of the four strains displayed numerous variations in comparison to the vaccine strains currently used in Egypt. In addition, most of these variations were present in prominent antigenic positions in the VP1 protein. These findings raise a crucial need to validate the protective potential of the vaccine strains against the newly emerging FMDV field strains and to update the vaccination strategy accordingly.

Despite the critical role of the Anopheles innate immune system in defending against Plasmodium infection, there is still limited information about the key immune mechanisms in Anopheles. This review assesses recent findings on the expression characteristics of immune-related genes in Anopheles following exposure to Plasmodium. A literature review, unrestricted by publication date, was conducted to evaluate immune-related gene expression in different organs of Anopheles after Plasmodium infection. Mosquito immune responses in the midgut are essential for reducing parasite populations. Additionally, innate immune responses in the salivary glands and hemocytes circulating in the hemocoel play key roles in defense against the parasite. Transcriptomic analysis of the mosquito's innate immune response to Plasmodium infection provides valuable insights into key immune mechanisms in mosquito defense. A deeper understanding of immune mechanisms in different organs of Anopheles following Plasmodium infection will aid in discovering critical targets for designing novel control strategies.

Mosquitoes are medically important insects, and accurate species identification is crucial to understanding vector biology, forming the cornerstone of successful vector control programs. Identification is difficult owing to morphologically similar species. Wing morphometrics can provide a simple, fast, and accurate way to classify species, and using it as a method to differentiate vector species among its cryptic congeners has been underexplored. Using a total of 227 mosquitoes and 20 landmarks per specimen, we demonstrated the utility of wing morphometrics in differentiating species two groups occurring in sympatry – Culex (Culex) vishnui group and Culex (Lophoceraomyia) subgenus, as well as explored population-level variation in the wing shape of Aedes albopictus across habitats. Cytochrome oxidase subunit I (COI) gene region was sequenced to validate the morphological and morphometric identification. Procrustes ANOVA regression and CVA based on wing shape reflected that the wing landmarks across all species differed significantly, and leave-one-out cross validation revealed an overall high accuracy of >97% for the two Culex groups. Wing morphometrics uncovered population-level variation within Aedes albopictus, but cross validation accuracy was low. Overall, we show that wing geomorphometric analysis is able to resolve cryptic Culex species (including vectors) occurring sympatrically, and is a robust tool for identifying mosquitoes reliably.

Bacterial responses to continuously changing environments are addressed through modulation of gene expression at the level of transcription initiation, RNA processing and/or decay. Ribonucleases (RNases) are hydrolytic or phosphorolytic enzymes involved in a majority of RNA metabolism reactions. RNases play a crucial role in RNA degradation, either independently or in collaboration with various trans-acting regulatory factors. The genus Mycobacterium consists of five subgenera: Mycobacteroides, Mycolicibacterium, Mycobacterium, Mycolicibacter and Mycolicibacillus, which include 63 fully sequenced species (pathogenic/non-pathogenic) to date. These include 13 different RNases, among which 5 are exonucleases (RNase PH, PNPase, RNase D, nano-RNases and RNase AS) and 8 are endonucleases (RNase J, RNase H, RNase P, RNase III, RNase BN, RNase Z, RNase G and RNase E), although RNase J and RNase BN were later identified to have exoribonuclease functions also. Here, we provide a detailed comparative insight into the Escherichia coli and mycobacterial RNases with respect to their types, phylogeny, structure, function, regulation and mechanism of action, with the main emphasis on RNase E. Among these 13 different mycobacterial RNases, 10 are essential for cell survival and have diverse structures hence, they are promising drug targets. RNase E is also an essential endonuclease that is abundant in many bacteria, forms an RNA degradosome complex that controls central RNA processing/degradation and has a conserved 5′ sensor domain/DNase-I like region in its RNase domain. The essential mycobacterial RNases especially RNase E provide a potential repertoire of drug targets that can be exploited for inhibitor/modulator screening against many deadly mycobacterial diseases.

Priestia is a genus that was renamed from the genus Bacillus based on the conserved signature indels (CSIs) in protein sequences that separate Priestia species from Bacillus, with the latter only including species closely related to B. subtilis and B. cereus. Diagnosis of anthrax, a zoonotic disease, is implicated by tripartite anthrax virulence genes (lef, pagA, and cya) and poly-γ-D-glutamic acid capsular genes cap-ABCDE of Bacillus anthracis. Due to the amplification of anthrax virulence genes in Priestia isolates, the search for homologous anthrax virulence genes within the Priestia genomes (n = 9) isolated from animal blood smears was embarked upon through whole genome sequencing. In silico taxonomic identification of the isolates was conducted using genome taxonomy database (GTDB), average nucleotide identity (ANI), and multi-locus sequence typing (MLST), which identified the genomes as P. aryabhattai (n = 5), P. endophytica (n = 2) and P. megaterium (n = 2). A pan-genome analysis was further conducted on the Priestia genomes, including the screening of virulence, antibiotic resistance genes and mobile genetic elements on the sequenced genomes. The oligoribonuclease NrnB protein sequences showed that Priestia spp. possess a unique CSI that is absent in other Bacillus species. Furthermore, the CSI in P. endophytica is unique from other Priestia spp. Pan-genomic analysis indicates that P. endophytica clusters separately from P. aryabhattai and P. megaterium. In silico BLASTn genome analysis using the SYBR primers, Taqman probes and primers that target the chromosomal marker (Ba-1), protective antigen (pagA), and lethal factor (lef) on B. anthracis, showed partial binding to Priestia regions encoding for hypothetical proteins, pyridoxine biosynthesis, hydrolase, and inhibitory proteins. The antibiotic resistance genes (ARG) profile of Priestia spp. showed that the genomes contained no more than two ARGs. This included genes conferring resistance to rifamycin and fosfomycin on P. endophytica, as well as clindamycin on P. aryabhattai and P. megaterium. Priestia genomes lacked B. anthracis plasmids and consisted of plasmid replicon types with unknown functions. Furthermore, the amplification of Priestia strains may result in false positives when qPCR is used to detect the virulence genes of B. anthracis in soil, blood smears, and/or environmental samples.

Background

The Beijing genotype of Mycobacterium tuberculosis (Mtb) has sparked debate regarding its virulence and transmissibility. This study contributes to this discussion by assessing its effect on the risk of latent tuberculosis infection (LTBI), active tuberculosis (TB) disease among contacts, and clustering of known TB cases.

Methods

We conducted a retrospective cohort study using the records of 4457 culture-confirmed TB patients and their contacts (20,448) reported to the Florida Department of Health between 2009 and 2023. Univariate and multivariate analyses were used to evaluate the effect of the Beijing strain on LTBI, active TB risk among contacts, and case clustering.

Results

Our study revealed no significant difference in transmissibility between the Beijing and non-Beijing genotypes among contacts. LTBI prevalence was 19.9%, slightly higher in non-Beijing than Beijing genotypes (20.2% vs. 15.5%, p < 0.001). The prevalence of active TB was 1.8%, with no significant difference between the Beijing and non-Beijing genotypes (1.4% vs. 1.8%, p = 0.296). Increased LTBI risk was associated with older age, male sex, Hispanic ethnicity, multidrug-resistant TB exposure, household exposure, and a longer exposure duration. Active TB risk was higher for males, HIV-positive individuals, and contacts with more prolonged exposure to index cases. The Beijing genotype was associated with increased TB case clustering (aOR = 1.98, 95%CI: 1.53, 2.55, p < 0.001) as compared to the non-Beijing genotypes. US birthplace (aOR = 2.75, 95%CI: 2.37, 3.19, p < 0.001), pulmonary disease (aOR = 1.27, 95%CI: 1.04, 1.56, p < 0.020), cavitary TB (aOR = 1.25, 95% CI: 1.08, 1.44, p < 0.003), previous year alcohol use (aOR = 1.68, 95%CI: 1.38, 2.04, p < 0.001), and recreational drug use (aOR = 1.32, 95%CI: 1.04, 1.67, p < 0.024) were also associated with an increased risk of TB case clustering.

Conclusion

While the Beijing genotype did not increase the risk of LTBI or active TB among contacts, it showed a higher tendency for case clustering. Hence, interventions should prioritize populations where this genotype is prevalent.

Background

To investigate the causal relationship between human papillomavirus (HPV) and lung cancer, we conducted a study using the two-sample Mendelian randomization (TSMR).

Method

Data from genome-wide association studies (GWAS) were analyzed with HPV E7 Type 16 and HPV E7 Type 18 as exposure factors. The outcome variables included lung cancer, small cell lung cancer, adenocarcinoma and squamous cell lung cancer. Causality was estimated using inverse variance weighted (IVW), MR-Egger and weighted median methods. Heterogeneity testing, sensitivity analysis, and multiple validity analysis were also performed..

Results

The results showed that HPV E7 Type 16 infection was associated with a higher risk of squamous cell lung cancer (OR = 7.69; 95% CI:1.98–29.85; p = 0.0149). HPV E7 Type 18 infection significantly increased the risk of lung adenocarcinoma (OR = 0.71; 95% CI: 0.38–1.31; p = 0.0079) and lung cancer (OR = 7.69; 95% CI:1.98–29.85; p = 0.0292). No significant causal relationship was found between HPV E7 Type 16 and lung adenocarcinoma, lung cancer, or small cell lung carcinoma, and between HPV E7 Type 18 and squamous cell lung cancer or small cell lung carcinoma.

Conclusions

This study has revealed a causal relationship between HPV and lung cancers. Our findings provide valuable insights for further mechanistic and clinical studies on HPV-mediated cancer.