Microbiology and Immunology最新文献

Cover photograph: Representation of the E6 + Lumacaftor (ZINC000064033452) complex. The hydrogen bonds formed (yellow dotted lines), the distance in Å of these interactions, and the residues that interact with the drug or are part of the binding site were highlighted. Microbiol Immunol: 68:414-426. Article link here

Staphylococcus aureus is a versatile pathogen capable of causing a wide range of infections, from minor skin infections to life-threatening invasive diseases. The pathogenicity of S. aureus is attributed to its ability to produce various virulence factors, including adhesion and biofilm-related proteins. Understanding the prevalence and distribution of these genes among S. aureus isolates from different sources is crucial for devising effective strategies to combat biofilm-associated contamination. In this study, we conducted a comprehensive network meta-analysis to assess the prevalence of adhesion and biofilm-related genes in S. aureus isolates and investigate the impact of the isolate source on their occurrence. A systematic search of multiple databases was performed, and a total of 53 relevant studies were included. The prevalence of adhesion and biofilm-related genes in S. aureus isolates was determined, with the highest prevalence observed for clfB (p-estimate = 85.4, 95% confidence interval [CI] 78–90.6), followed by eno (p-estimate = 81.1, 95% CI 61.7–91.9), and icaD (p-estimate = 77, 95% CI 68.6–83.6). Conversely, bap and bbp genes exhibited the lowest prevalence rates (p-estimate = 6.7 and 18.7, respectively). The network meta-analysis allowed us to examine the pairwise co-study of adhesion and biofilm-related genes in S. aureus isolates. The most frequently co-studied gene pairs were icaA-icaD (30 times) and fnbA-fnbB (25 times). Subgroup analysis showed that the occurrence of icaC and icaB genes was significantly lower in animal isolates compared to human and food isolates (p < 0.05). It is worth noting that there was limited data available for the analysis of sasG, bbp, bap, eno, and fib genes. In conclusion, the study revealed varying prevalence rates of adhesion and biofilm-related genes in S. aureus isolates. Genes such as clfB, eno, and icaD were found to be highly prevalent, while bap and bbp were less common. Limited existing data on the prevalence of genes like sasG, bbp, bap, eno, and fib highlights the need for further research to determine their exact prevalence rates. Our results contribute to a better understanding of S. aureus pathogenesis and can facilitate the development of effective strategies for the prevention and treatment of S. aureus infections.

Hepatitis B virus (HBV) infection is a serious global health problem causing acute and chronic hepatitis and related diseases. Approximately, 296 million patients have been chronically infected with the virus, leading to cirrhosis and hepatocellular carcinoma. Although HBV polymerase (HBVpol, pol) plays a pivotal role in HBV replication and must be a definite therapeutic target. The problems are that the detailed functions and intracellular dynamics of HBVpol remain unclear. Here, we constructed two kinds of tagged HBVpol, PA-tagged and HiBiT-tagged pol, and the HBV-producing vectors. Each PA tag and HiBiT tag were inserted into N-terminus of spacer region on HBVpol open reading frame. Transfection of the plasmids into HepG2 cells led to production of HBV. These tagged HBVpol were detectable in HBV replicating cells and pol-HiBiT enabled quantitative analysis. Furthermore, these recombinant HBV were infectious to primary human hepatocytes. Thus, we successfully designed infectious and replication-competent recombinant HBV harboring detectable tagged HBVpol. Such infectious recombinant HBV will provide a novel tool to study HBVpol dynamics and develop new therapeutics against HBV.

Functional constipation (FC) is a common digestive disorder that affects patients' quality of life and is closely associated with intestinal tumors. This study used a cross-sectional design to assess the changes of intestinal flora and metabolites in different severities of FC patients through 16S rRNA sequencing and metabolomics analysis. Results showed that patients with severe FC had significantly higher clinical and anxiety scores compared to those in the mild and moderate groups. The species richness of intestinal microorganisms in the severe FC group was also significantly higher, and obvious differences in the flora composition existed. Specifically, the Bacteroidota was more abundant in the severe FC group, which was a characteristic feature distinguishing severe FC. Metabolomic analyses also revealed metabolite differences among patients with mild-to-moderate and severe FC, with the severe FC group showing increased enrichment in L-isoleucine biosynthesis and glycolysis metabolic pathways. The short-chain fatty acid–targeted metabolome suggested that a decrease in butyric acid might be related to worsening constipation. This study suggests that specific flora and metabolic pathways could serve as potential diagnostic and therapeutic targets, thereby contributing to the development of new diagnostic and therapeutic approaches to improve the quality of life and therapeutic outcomes for FC patients.

In this study, we have established a Staphylococcus aureus RpoB H481Y mutant strain and demonstrated that it is sensitive to menadione or hydrogen peroxide-induced oxidative stress and exhibits reduced virulence against a silkworm infection model. Furthermore, the reduced virulence of the RpoB H481Y mutant was abrogated in the presence of N-acetylcysteine, a reactive oxygen species scavenger. These results suggest that oxidative stress sensitivity caused by the RpoB H481Y rifampicin resistance mutation attenuates the virulence of S. aureus.

Orientia tsutsugamushi (OT) is an obligate intracellular bacterium transmitted by larval trombiculid mites, responsible for scrub typhus in humans. In Japan, approximately 500 human cases are reported annually, with six major serotypes identified as Kato, Karp, Gilliam, Irie/Kawasaki, Shimokoshi, and Hirano/Kuroki. However, the prevalence of OT in Yamaguchi prefecture remains largely unknown. This study aimed to investigate the prevalence and serotypes of OT in wild rodents collected from eight locations within the prefecture. DNA was extracted from spleen and liver samples of 135 wild rodents collected between 2015 and 2024, and PCR was conducted to detect OT targeting the 56 kDa type-specific antigen gene. As a result, five individuals (3.7%) were detected positive for OT DNA. OT was successfully isolated from two of the five rodents and characterized by multi-locus sequence analysis (MLSA) based on 11 housekeeping genes. The MLSA results indicated that both isolates clustered with OT strain Ikeda (JG serotype). Additionally, we performed a serological test on 117 serum samples from wild rodents using the indirect immune peroxidase test. The results showed that 59.8% (n = 70/117) of the rodents had antibodies against OT, with 73% (n = 51/70) showing the highest titer against the OT strains Gilliam (Gilliam serotype) and Ikeda (JG serotype), known to be transmitted by Leptotrombidum pallidum mites. Overall, the present study identified the OT serotypes and potential primary vector species in Yamaguchi prefecture, emphasizing the need for further surveillance, particularly, in humans.

Asthma, an allergic disease of the airways, is a risk factor for severity of common respiratory viral infections; however, the relationship between asthma and severity in COVID-19 remains unclear. Here, we examined the effects of SARS-CoV-2 (Omicron BA.5 strain) infection in a mouse model of airway allergy. First, stimulation of allergic mice with OVA resulted in the appearance of ACE2-negative mucus-secreting goblet cells in the bronchiolar region, and an increase in the number of ACE2-expressing cells in the alveoli. As a result, ACE2-expressing cells, which are susceptible to SARS-CoV-2, were limited to the distal portion of the bronchioles while they increased in the alveolar area. After viral infection, the peak infectious viral load in the OVA group was 100-fold lower than that in the phosphate buffered saline (PBS) group; however, clearance of viral RNA from the upper/lower airways was delayed. There were notable differences in acquisition of nsp5 and nsp6 mutations by the Omicron BA.5 strain recovered from BALF samples obtained from the OVA and PBS groups. Immune responses associated with viral clearance were essentially the same, but expression of granulocyte-associated chemokines was higher, M2 macrophage responses were predominant, and the higher spike-specific IgG1/IgG2a ratio in the OVA group post-infection. Infection localized in the alveolar region earlier in the OVA group, resulting in more severe alveolar damage than in the PBS group. These data suggest a Th2-shifted immune background and altered localization of SARS-CoV-2 susceptible cells in mice with OVA-induced airway allergy, which reflect Omicron BA.5 infection dynamics, viral mutations, and immunopathology.