XIAP-mediated degradation of IFT88 disrupts HSC cilia to stimulate HSC activation and liver fibrosis.

Activation of hepatic stellate cells (HSCs) plays a critical role in liver fibrosis. However, the molecular basis for HSC activation remains poorly understood. Herein, we demonstrate that primary cilia are present on quiescent HSCs but exhibit a significant loss upon HSC activation which correlates with decreased levels of the ciliary protein intraflagellar transport 88 (IFT88). Ift88-knockout mice are more susceptible to chronic carbon tetrachloride-induced liver fibrosis. Mechanistic studies show that the X-linked inhibitor of apoptosis (XIAP) functions as an E3 ubiquitin ligase for IFT88. Transforming growth factor-ß (TGF-ß), a profibrotic factor, enhances XIAP-mediated ubiquitination of IFT88, promoting its proteasomal degradation. Blocking XIAP-mediated IFT88 degradation ablates TGF-ß-induced HSC activation and liver fibrosis. These findings reveal a previously unrecognized role for ciliary homeostasis in regulating HSC activation and identify the XIAP-IFT88 axis as a potential therapeutic target for liver fibrosis.

Global spread characteristics of CTX-M-type extended-spectrum ß-lactamases: A genomic epidemiology analysis.

BACKGROUND: Extended-spectrum ß-lactamases (ESBLs) producing bacteria have spread worldwide and become a global public health concern. Plasmid-mediated transfer of ESBLs is an important route for resistance acquisition. METHODS: We collected 1345 complete sequences of plasmids containing CTX-Ms from public database. The global transmission pattern of plasmids and evolutionary dynamics of CTX-Ms have been inferred. We applied the pan-genome clustering based on plasmid genomes and evolution analysis to demonstrate the transmission events. FINDINGS: Totally, 48 CTX-Ms genotypes and 186 incompatible types of plasmids were identified. The geographical distribution of CTX-Ms showed significant differences across countries and continents. CTX-M-14 and CTX-M-55 were found to be the dominant genotypes in Asia, while CTX-M-1 played a leading role in Europe. The plasmids can be divided into 12 lineages, some of which forming distinct geographical clusters in Asia and Europe, while others forming hybrid populations. The Inc types of plasmids are lineage-specific, with the CTX-M-1_IncI1-I (Alpha) and CTX-M-65_IncFII (pHN7A8)/R being the dominant patterns of cross-host and cross-regional transmission. The IncI-I (Alpha) plasmids with the highest number, were presumed to form communication groups in Europe-Asia and Asia-America-Oceania, showing the transmission model as global dissemination and regional microevolution. Meanwhile, the main kinetic elements of blaCTX-Ms showed genotypic preferences. ISEcpl and IS26 were most frequently involved in the transfer of CTX-M-14 and CTX-M-65, respectively. IS15 has become a crucial participant in mediating the dissemination of blaCTX-Ms. Interestingly, blaTEM and blaCTX-Ms often coexisted in the same transposable unit. Furthermore, antibiotic resistance genes associated with aminoglycosides, sulfonamides and cephalosporins showed a relatively high frequency of synergistic effects with CTX-Ms. CONCLUSIONS: We recognized the dominant blaCTX-Ms and mainstream plasmids of different continents. The results of this study provide support for a more effective response to the risks associated with the evolution of blaCTX-Ms-bearing plasmids, and lay the foundation for genotype-specific epidemiological surveillance of resistance, which are of important public health implications.

The definition and global epidemiology of nonmobile colistin resistance (NMCR-3) determinants in Aeromonas from 1968 to 2022.

Polymyxins are the last line of defense in infections caused by multidrug-resistant Gram-negative bacteria. The chromosomal EptA in Aeromonas genus was defined as a nonmobile colistin resistance determinant 3 (NMCR-3). A total of 14 NMCR-3 genotypes were identified. The global prevalence of Aeromonas-borne NMCRs and MCRs indicates an increasing trend from 1968 to 2022. And an index of resistance risk, i.e, the ratio of η = MCR/NMCR, was proposed to evaluate the propagation potential of NMCR-3. The colistin resistance in North America and Europe faced a high risk of increasing incidence of MCR since large proportions of NMCR-3 variants disseminated from Aeromonas sources. We concluded that NMCR-3 variants act natural progenitors for MCR-3/5/7, and the future MCR variant(s) will most likely be MCR-5 or MCR-7, which is also an early warning of next MCR(s) emerging in Aeromonas.

Nonsense-mediated mRNA decay promote C2C12 cell proliferation by targeting PIK3R5.

Nonsense mediated mRNA decay (NMD) is a highly conserved RNA quality control system, which can specifically clear abnormal mRNA and play an important role in tumorigenesis. Myoblast proliferation plays an important role in the repair of skeletal muscle injury and the development of myosarcoma, and is controlled by a variety of transcription factors and signals. The molecular mechanism by which NMD regulates the proliferation of myoblast cells is not completely clear. In this study, we found that the NMD activity of skeletal muscle is high in 1-week-old mice but decreases gradually with age, corresponding to a weakening capacity for muscle growth and regeneration. Here, we provide evidence that NMD plays an important role in myoblast proliferation and apoptosis. In addition, we found that PIK3R5 is an NMD substrate gene which can inhibit AKT activity and C2C12 cell proliferation. Therefore, NMD can target PIK3R5 to enhance AKT activity, which in turn promotes C2C12 cell proliferation. This study provides new insights into NMD regulatory mechanisms in muscular development and into potential novel therapeutic strategies for muscle atrophy.

The Potential of Cylindromatosis (CYLD) as a Therapeutic Target in Oxidative Stress-Associated Pathologies: A Comprehensive Evaluation.

Oxidative stress (OS) arises as a consequence of an imbalance between the formation of reactive oxygen species (ROS) and the capacity of antioxidant defense mechanisms to neutralize them. Excessive ROS production can lead to the damage of critical biomolecules, such as lipids, proteins, and DNA, ultimately contributing to the onset and progression of a multitude of diseases, including atherosclerosis, chronic obstructive pulmonary disease, Alzheimer's disease, and cancer. Cylindromatosis (CYLD), initially identified as a gene linked to familial cylindromatosis, has a well-established and increasingly well-characterized function in tumor inhibition and anti-inflammatory processes. Nevertheless, burgeoning evidence suggests that CYLD, as a conserved deubiquitination enzyme, also plays a pivotal role in various key signaling pathways and is implicated in the pathogenesis of numerous diseases driven by oxidative stress. In this review, we systematically examine the current research on the function and pathogenesis of CYLD in diseases instigated by oxidative stress. Therapeutic interventions targeting CYLD may hold significant promise for the treatment and management of oxidative stress-induced human diseases.

Multilocus sequence analysis for the taxonomic updating and identification of the genus Proteus and reclassification of Proteus genospecies 5 O'Hara et al. 2000, Proteus cibarius Hyun et al. 2016 as later heterotypic synonyms of Proteus terrae Behrendt et al. 2015.

BACKGROUND: Members of the genus Proteus are mostly opportunistic pathogens that cause a variety of infections in humans. The molecular evolutionary characteristics and genetic relationships among Proteus species have not been elucidated to date. In this study, we developed a multilocus sequence analysis (MLSA) approach based on five housekeeping genes (HKGs) to delineate phylogenetic relationships of species within the genus Proteus. RESULTS: Of all 223 Proteus strains collected in the current study, the phylogenetic tree of five concatenated HKGs (dnaJ, mdh, pyrC, recA and rpoD) divided 223 strains into eleven clusters, which were representative of 11 species of Proteus. Meanwhile, the phylogenetic trees of the five individual HKGs also corresponded to that of the concatenated tree, except for recA, which clustered four strains at an independent cluster. The evaluation of inter- and intraspecies distances of HKG concatenation indicated that all interspecies distances were significantly different from intraspecies distances, which revealed that these HKG concatenations can be used as gene markers to distinguish different Proteus species. Further web-based DNA-DNA hybridization estimated by genome of type strains confirmed the validity of the MLSA, and each of eleven clusters was congruent with the most abundant Proteus species. In addition, we used the established MLSA method to identify the randomly collected Proteus and found that P. mirabilis is the most abundant species. However, the second most abundant species is P. terrae but not P. vulgaris. Combined with the genetic, genomic and phenotypic characteristics, these findings indicate that three species, P. terrae, P. cibarius and Proteus genospecies 5, should be regarded as heterotypic synonyms, and the species should be renamed P. terrae, while Proteus genospecies 5 has not been named to date. CONCLUSIONS: This study suggested that MLSA is a powerful method for the discrimination and classification of Proteus at the species level. The MLSA scheme provides a rapid and inexpensive means of identifying Proteus strains. The identification of Proteus species determined by the MLSA approach plays an important role in the clinical diagnosis and treatment of Proteus infection.

Proteus alimentorum sp. nov., isolated from pork and lobster in Ma'anshan city, China.

Two strains of Gram-stain-negative, facultatively anaerobic short-rod bacteria were recovered from two different food samples in Ma'anshan city, Anhui province, China in 2008. The bacteria were characterized in a polyphasic taxonomic study that included phenotypic, phylogenetic and genotypic methodologies. Phylogenetic analysis of the 16S rRNA gene demonstrated that the two strains belonged to the genus Proteus and were most similar to Proteus vulgaris ATCC 29905T with a score of 99.7 %. Phylogenetic analysis of the rpoB gene placed the two strains into a cluster with a distinctly interspecies phylogenetic branch that was clearly separated from six type strains of the genus Proteus, with the most closely related species being Proteus mirabilis ATCC 29906T. In silico genomic comparisons, including in silico DNA-DNA hybridization (isDDH) and average nucleotide identity (ANI) analysis showed that the representative strain, 08MAS0041T, and all six Proteus species share less than 70 % isDDH and have a 95 % ANI cutoff level, supporting the designation of the two strains as a novel species of the genus Proteus. The predominant cellular fatty acids of strain 08MAS0041T were C16 : 0 (24.8 %), C16 : 1ω7c/16 : 1ω6c (16.5 %), C18 : 1ω6c/C18 : 1ω7c (14.5 %), C17 : 0 cyclo (12.6 %) and C16 : 1iso I/C14 : 0 3-OH (10.6 %). The analysis of biochemical, phylogenetic and genomic data confirmed that the two strains were clearly different from all recognized species of the genus Proteus and represent a novel Proteus species, for which the name Proteus alimentorum sp. nov. is proposed. The type strain is 08MAS0041T (=DSM 104685T=CGMCC 1.15939T).

Proteus columbae sp. nov., isolated from a pigeon in Ma'anshan, China.

A Gram-negative, facultatively anaerobic bacillus, strain 08MAS2615T, was isolated from the flesh of a pigeon specimen collected in Ma'anshan, Anhui province, China. Phylogenetic analysis of 16S rRNA gene sequences confirmed that strain 08MAS2615T belonged to the genus Proteus, and formed an independent branch which was clearly separated from the other six known species of Proteus. Strain 08MAS2615T was more closely related to Proteus vulgaris ATCC 29905T and Proteus penneri NCTC 12737T than other Proteus species. Similar independent phylogenetic results were obtained using rpoB gene sequence analysis, whereas strain 08MAS2615T clustered near the species of Proteus cibarius JS9T and Proteus terrae N5/687T. Furthermore, the genome-wide core-single nucleotide polymorphism-based phylogenetic tree confirmed that strain 08MAS2615T formed a monophyletic and robust clade. Based on whole-genome sequences, the range of in silico DNA-DNA hybridization and average nucleotide identity between strain 08MAS2615T and the six Proteus species were 25.5-48.8 % and 82.8-92.9 %, respectively, less than the proposed cutoff level for species delineation, i.e. 70 and 95 %. In addition, the major cellular fatty acid profile of strain 08MAS2615T was C14 : 0 (12.4 %), C16 : 0 (23.8 %), C17 : 0cyclo (14.4 %), summed feature 2 (C16 : 1iso I/C14 : 0 3-OH) (11.0 %), summed feature 3 (C16 : 1ω7c/16 : 1ω6c) (18.5 %) and summed feature 8 (C18 : 1ω6c) (18.6 %). On the basis of these results, strain 08MAS2615T represents a novel species of the genus Proteus, for which the name Proteuscolumbae sp. nov. is proposed with strain 08MAS2615T (=DSM 104686T=CGMCC 1.15982T) designated as the species type strain.

Epidemiology and molecular characterization of CTX-M-type ESBLs producing Escherichia coli isolated from clinical settings.

OBJECTIVES: Recently, blaCTX-Ms have become the dominant ESBLs for E. coli strains worldwide. We aim to provide a systematic study on the relationships between sequence types (STs), clinical origins, and the blaCTX-Ms genotypes of E. coli strains. METHODS: Totally, 1005 complete sequences of clinical E. coli were collected from NCBI. Multilocus sequence typing (MLST) and antibiotic resistance genes screening were performed. RESULTS: Faeces (26.27%), urine (16.02%), and blood (8.26%) were shown to be the main sources of clinical E. coli isolates. The isolates belong to 153 STs and 26 clonal complexes (CCs). The most prevalent STs were ST2 (11.3%), ST43 (8.6%), and ST8 (5.7%). The positive rate for blaCTX-Ms was 34.7%. Different samples showed significantly different blaCTX-Ms positive rates (P<0.05). The main genotypes were blaCTX-M-55-like (47.6%), blaCTX-M-1-like (31.8%), and blaCTX-M-2-like (22.1%). The majority of ST2 strains had blaCTX-M-55-like genes. In ST8 strains, there was a homogeneous distribution of blaCTX-M-9, blaCTX-M-65, blaCTX-M-55, blaCTX-M-2, and blaCTX-M-1. Only ST43 strains exhibited the presence of blaCTX-M-79. The blaCTX-Ms showed a pattern of cross-continental transmission with intra-regional spread. Among the 349 blaCTX-Ms-producing E. coli strains, 148 strains also carried carbapenem resistance genes, including blaNDM (119, 34.1%), blaKPC (16, 4.6%), blaOXA-48 (9, 2.6%) and blaIMP (4, 1.1%). Also, 81 strains carried the mcr gene (23.2%). CONCLUSIONS: E. coli has become increasingly rich in blaCTX-Ms genotypes. Our findings about the connection between E. coli STs and blaCTX-Ms can be utilized to identify E. coli strains with high potential to spread drug resistance in the future.

Prevalence and molecular characteristics of Shewanella infection in diarrhea patients in Beijing, China 2017-2019.

Introduction: Shewanella is an important opportunistic pathogen distributed in marine environments that has caused an increasing number of clinical infections. However, there are few reports on the distribution and characteristics of Shewanella in the diarrheal pathogen spectrum. In this study, we have systematically described the prevalence of Shewanella infections in diarrhea patients in Beijing, China 2017-2019, and genome characteristics and antimicrobial susceptibility of Shewanella isolates. Methods: Stool samples were collected from diarrhea patients in a surveillance project from 2017 to 2019. Shewanella strains were isolated, and identified using VITEKR 2 COMPACT and MALDI-TOF MS. Average nucleotide identity (ANI) analysis, multi-locus sequence typing (MLST), phylogenetic analysis, virulence-associated genes and antimicrobial resistance genes analysis were used for genome characteristics description. The antibiotic susceptibility test was performed with microbroth dilution method. Results: 1104 fecal samples were collected, and the Shewanella detection rate was 2.36% (26/1104). The main manifestations of infection caused by Shewanella spp. were diarrhea (100%, 26/26), abdominal pain (65.38%, 17/26), and vomiting (38.46%, 10/26). The 26 isolates were classified into 3 species (S. algae (n = 18), S. indica (n = 5), and S. chilikensis (n = 3)) and 22 sequence types. Core genome single nucleotide polymorphism-based evolutionary tree identified three clone groups corresponding to three infection events in the same months in 2017 and 2019. The putative virulence-associated gene pool consisted of 56 potential virulence genes, including 19 virulence gene factors. The resistance rates of the 26 isolates to 17 antibiotics from high to low were as follows: polymyxin E (76.92%), cefotaxime (57.69%), ampicillin (50%), ampicillin-sulbactam (34.62%), nalidixic acid (15.38%), ciprofloxacin (11.54%), selectrin (3.846%,1/26), and tetracycline (3.846%, 1/26). The rate of multidrug resistance was 38.46% (10/26). Discussion: Monitoring for Shewanella spp. should be added to the routine surveillance of infectious diarrhea during the epidemic season.

Genomic insights into the evolution, pathogenicity, and extensively drug-resistance of emerging pathogens Kluyvera and Phytobacter.

Introduction: Kluyvera is a Gram-negative, flagellated, motile bacillus within the Enterobacteriaceae. The case reports of clinical infections shed light on the importance of this organism as an emerging opportunistic pathogen. The genus Phytobacter, which often be misidentified with Kluyvera, is also an important clinically relevant member of the Enterobacteriaceae. However, the identification of Kluyvera and Phytobacter is problematic, and their phylogenetic relationship remains unclear. Methods: Here, 81 strains of Kluyvera and 16 strains of Phytobacter were collected. A series of comparative genomics approaches were applied to the phylogenetic relationship reconstruction, virulence related genes profiles description, and antibiotic resistance genes prediction. Results: Using average nucleotide identity (ANI) and in silico DNA-DNA hybridization (isDDH), we offered reliable species designations of 97 strains, in which 40 (41.24%) strains were incorrectly labeled. A new Phytobacter genomospecies-1 were defined. Phytobacter and Kluyvera show great genome plasticity and inclusiveness, which may be related to their diverse ecological niches. An intergenomic distances threshold of 0.15875 was used for taxonomy reassignments at the phylogenomic-group level. Further principal coordinates analysis (PCoA) revealed 11 core genes of Kluyvera (pelX, mdtL, bglC, pcak-1, uhpB, ddpA-2, pdxY, oppD-1, cptA, yidZ, csbX) that could be served as potential identification targets. Meanwhile, the Phytobacter specific virulence genes clbS, csgA-C, fliS, hsiB1_vipA and hsiC1_vipB, were found to differentiate from Kluyvera. We concluded that the evolution rate of Kluyvera was 5.25E-6, approximately three times higher than that of Phytobacter. Additionally, the co-existence of ESBLs and carbapenem resistance genes were present in approximately 40% strains, suggesting the potential development of extensively drug-resistant or even fully drug-resistant strains. Discussion: This work provided a better understanding of the differences between closely related species Kluyvera and Phytobacter. Their genomes exhibited great genome plasticity and inclusiveness. They not only possess a potential pathogenicity threat, but also a risk of multi-drug resistance. The emerging pathogens Kluyvera and Phytobacter warrant close attention.

Genome-wide expanding of genetic evolution and potential pathogenicity in Vibrio alginolyticus.

Vibrio alginolyticus, an emergent species of Vibrio genus, exists in aquatic and marine environments. It has undergone genetic diversification, but its detailed genomic diversity is still unclear. Here, we performed a multi-dimensional comparative genomic analysis to explore the population phylogeny, virulence-related genes and potential drug resistance genes of 184 V. alginolyticus isolates. Although genetic diversity is complex, we analysed the population structure using three sub-datasets, including the subdivision for three lineages into sublineages and the distribution of strains in the marine ecological niche. Accessory genes, most of which reclassified V. alginolyticus genomes as different but with relatively close affinities, were nonuniformly distributed among these isolates. We demonstrated that the spread of some post-evolutionary isolates (mainly L3 strains isolated from Chinese territorial seas) was likely to be closely related to human activities, whereas other more ancestral strains (strains in the L1 and L2) tended to be locally endemic and formed clonal complex groups. In terms of pathogenicity, the potential virulence factors were mainly associated with toxin, adherence, motility, chemotaxis, and the type III secretion system (T3SS). We also found five types of antibacterial drug resistance genes. The prevalence of ß-lactam resistance genes was 100%, which indicated that there may be a potential risk of natural resistance to ß-lactam drugs. Our study reveals insights into genomic characteristics, evolution and potential virulence-associated gene profiles of V. alginolyticus.

Capture of armA by a novel ISCR element, ISCR28.

ISCR28 is a fully functional and active member of the IS91-like family of insertion sequences. ISCR28 is 1,708-bp long and contains a 1,293-bp long putative open reading frame that codes a transposase. Sixty ISCR28-containing sequences from GenBank generated 27 non-repeat genetic contexts, all of which represented naturally occurring biological events that had occurred in a wide range of gram-negative organisms. Insertion of ISCR28 into target DNA preferred the presence of a 5'-GXXT-3' sequence at its terIS (replication terminator) end. Loss of the first 4 bp of its oriIS (origin of replication) likely caused ISCR28 to be trapped in ISApl1-based transposons or similar structures. Loss of terIS and fusion with a mobile element upstream likely promoted co-transfer of ISCR28 and the downstream resistance genes. ArmA and its downstream intact ISCR28 can be excised from recombinant pKD46 plasmids forming circular intermediates, further elucidating its activity as a transposase.

Screening of Staphylococcus aureus for Disinfection Evaluation and Transcriptome Analysis of High Tolerance to Chlorine-Containing Disinfectants.

The nonstandard use of disinfectants can lead to the disinfectant resistance of bacteria and even increase antibiotic resistance. However, compared with the study of antibiotic resistance, studies of bacterial resistance to disinfectants are relatively few in number. In this study, we explored the standard strain screening procedure for the evaluation of disinfection efficacy. Staphylococcus aureus strains with different sources and substrates were selected from the National Pathogen Resource Center of China and screened the standard strains that could evaluate the long-term bacteriostatic effect of the chlorine-containing disinfectants through the determination of the physical properties, genome-based safety evaluation, and disinfection test evaluation. In this process, one S. aureus strain was more resistant to the long-term bacteriostasis of chlorine-containing disinfectants than the other strains. This strain and the standard strain ATCC 6538 were cultured in the medium containing a low concentration of chlorine-containing disinfectant synchronously. Then, comparative transcriptome analysis was carried out to investigate the potential mechanism of a high tolerance to chlorine-containing disinfectants. The pathway of significant differential expression is related to the oxocarboxylic acid metabolic mechanism, amino acid metabolic mechanism, and pyrimidine mechanism, which may be the molecular mechanism of S. aureus evolution to adapt to chlorine-containing disinfectants. Our study established a technical process for screening and evaluating standard strains for disinfection, which also provided a reference for studying the bacterial evolution mechanism toward chlorine tolerance.

Vibrio metschnikovii as an emergent pathogen: analyses of phylogeny and O-antigen and identification of possible virulence characteristics.

Vibrio metschnikovii is an emergent pathogen that causes human infections which may be fatal. However, the phylogenetic characteristics and pathogenicity determinants of V. metschnikovii are poorly understood. Here, the whole-genome features of 103 V. metschnikovii strains isolated from different sources are described. On phylogenetic analysis V. metschnikovii populations could be divided into two major lineages, defined as lineage 1 (L1) and 2 (L2), of which L1 was more likely to be associated with human activity. Meanwhile, we defined 29 V. metschnikovii O-genotypes (VMOg, named VMOg1-VMOg29) by analysis of the O-antigen biosynthesis gene clusters (O-AGCs). Most VMOgs (VMOg1 to VMOg28) were assembled by the Wzx/Wzy pathway, while only VMOg29 used the ABC transporter pathway. Based on the sequence variation of the wzx and wzt genes, an in silico O-genotyping system for V. metschnikovii was developed. Furthermore, nineteen virulence-associated factors involving 161 genes were identified within the V. metschnikovii genomes, including genes encoding motility, adherence, toxins, and secretion systems. In particular, V. metschnikovii was found to promote a high level of cytotoxicity through the synergistic action of the lateral flagella and T6SS. The lateral flagellar-associated flhA gene played an important role in the adhesion and colonization of V. metschnikovii during the early stages of infection. Overall, this study provides an enhanced understanding of the genomic evolution, O-AGCs diversity, and potential pathogenic features of V. metschnikovii.

Genomic Characteristion of Opportunistic Pathogen Kluyvera Reveals a Novel CTX-M Subgroup.

A rising incidence of clinical infections has been caused by Kluyvera, a significant opportunistic pathogen. Meanwhile, Kluyvera acts as an important reservoir of blaCTX-Ms, which are the dominant genes of class A extended-spectrum ß-lactamases (ESBLs). In this work, 60 strains of Kluyvera were subjected to phylogenetic relationship reconstruction, antimicrobial susceptibility testing, and antibiotic resistance genes prediction. All mature blaCTX-Ms were gathered to perform subgroup reclassification. The findings demonstrate that Kluyvera has a large gene pool with significant genetic flexibility. Notably, 25% of strains showed simultaneous detection of ESBLs and carbapenem resistance genes. The genotypes of fourteen novel blaCTX-Ms were identified. A new subgroup classification approach for blaCTX-Ms was defined by using 20 amino acid site variants, which could split blaCTX-Ms into 10 subgroups. The results of the subgroup division were consistent with the phylogenetic clustering. More significantly, we proposed a novel blaCTX-M subgroup, KLUS, that is chromosomally encoded in K. sichuanensis and the new species put forward in this study, showing amino acid differences from the currently known sequences. Cloning and transformation tests demonstrated that the recipient bacteria had a robust phenotype of cefotaxime resistance. Closely related Kluyvera species had blaCTX-Ms in the same subgroup. Our research lays the groundwork for a deeper comprehension of Kluyvera and emphasizes how important a blaCTX-M reservoir it is. We provide an update on blaCTX-M subgroups reclassification from the aspects of phylogenetic relationship, amino acid differences, and the new subgroup KLUS, which needs to be strengthen monitored due to its strong resistance phenotype to cefotaxime.

Stenotrophomonas maltophilia complex: insights into evolutionary relationships, global distribution and pathogenicity.

Introduction: Stenotrophomonas maltophilia complex (Smc) comprises opportunistic Gram-negative bacilli responsible for various nosocomial infections. Limited data exists concerning its evolutionary lineage, global prevalence and pathogenicity. Methods: We conducted an extensive genomic analysis on 734 Smc genomes, of which 90 were newly sequenced and isolated from different patients. The species composition and evolutionary relationships of Smc were examined using core protein sequence analysis. Pathogenicity evaluation was used by assays for swimming motility, biofilm formation and identification of virulence factors. The broth microdilution method was used to evaluate the drug resistance spectrum of clinical isolates. Results: Phylogenetic analyses delineated 24 species-level clades, dominated by S. maltophilia (42.8%), S. sepilia (13.6%) and S. geniculata (9.9%). Geographically, strains were primarily distributed in Europe (34.2%), Asia (33.7%) and North America (24.0%), with intricate global distribution patterns. Meanwhile, 154 virulence-associated genes and 46 antimicrobial resistance genes within Smc were identified. These genes encoded span various functions, including motility, adherence, toxin, RND antibiotic efflux pumps, beta-lactamases and aminoglycoside-modifying enzymes. Moreover, significant variations were indicated in swimming motility and biofilm-forming capability across the different species, with S. sepilia exhibiting superior levels of both traits. Additionally, no statistically significant discrepancy was detected among Smc species to other antibiotics, despite the fact that all S. geniculata isolates were resistant to Ceftazidime and much higher than other species. Conclusion: Our findings indicate the need to pay increased attention to other mainstream species of Smc besides S. maltophilia in order to better manage Smc-related infections and tailor effective treatment strategies.

A Large Acute Gastroenteritis Outbreak Associated with Both Campylobacter coli and Human Sapovirus - Beijing Municipality, China, 2021.

What is already known about this topic?: Campylobacter is a significant foodborne pathogen that leads to global outbreaks of acute gastroenteritis (AGE) usually affecting less than 30 individuals. Human sapovirus (HuSaV) is an enteric virus responsible for sporadic cases and outbreaks of AGE worldwide. In a study conducted in Beijing, HuSaV detection ranked second after norovirus. What is added by this report?: We present a discussion of the first large-scale outbreak of AGE caused by both Campylobacter coli (C. coli) and HuSaV. The outbreak involved a total of 996 patients and exhibited two distinct peaks over a period of 17 days. Through case-control studies, we identified exposure to raw water from a secondary water supply system as a significant risk factor. Among 83 patients, 49 samples tested positive for C. coli, 39 samples tested positive for HuSaV, and 27 samples tested positive for both pathogens using real-time polymerase chain reaction detection. Furthermore, whole-genome sequencing of 17 C. coli isolates obtained from 17 patients revealed that all isolates belonged to a highly clonal strain of C. coli. What are the implications for public health practice?: Outbreaks of AGE resulting from multiple pathogen infections warrant increased attention. This report emphasizes the significance of ensuring the safety of drinking water, particularly in secondary supply systems.

Shewanella infection in humans: Epidemiology, clinical features and pathogenicity.

The genus Shewanella consists of Gram-negative proteobacteria that are ubiquitously distributed in environment. As the members of this genus have rapidly increased within the past decade, several species have become emerging pathogens worldwide, attracting the attention of the medical community. These species are also associated with severe community- and hospital-acquired infections. Patients infected with Shewanella spp. had experiences of occupational or recreational exposure; meanwhile, the process of infection is complex and the pathogenicity is influenced by a variety of factors. Here, an exhaustive internet-based literature search was carried out in PUBMED using terms "Achromobacter putrefaciens," "Pseudomonas putrefaciens," "Alteromonas putrefaciens" and "Shewanella" to search literatures published between 1978 and June 2022. We provided a comprehensive review on the epidemiology, clinical features and pathogenicity of Shewanella, which will contribute a better understanding of its clinical aetiology, and facilitate the timely diagnosis and effective treatment of Shewanella infection for clinicians and public health professionals.

Comparative Genomic Analysis Reveals Potential Pathogenicity and Slow-Growth Characteristics of Genus Brevundimonas and Description of Brevundimonas pishanensis sp. nov.

The genus Brevundimonas consists of Gram-negative bacteria widely distributed in environment and can cause human infections. However, the genomic characteristics and pathogenicity of Brevundimonas remain poorly studied. Here, the whole-genome features of 24 Brevundimonas type strains were described. Brevundimonas spp. had relatively small genomes (3.13 ± 0.29 Mb) within the family Caulobacteraceae but high G+C contents (67.01 ± 2.19 mol%). Two-dimensional hierarchical clustering divided those genomes into 5 major clades, in which clades II and V contained nine and five species, respectively. Interestingly, phylogenetic analysis showed a one-to-one match between core and accessory genomes, which suggested coevolution of species within the genus Brevundimonas. The unique genes were annotated to biological functions like catalytic activity, signaling and cellular processes, multisubstance metabolism, etc. The majority of Brevundimonas spp. harbored virulence-associated genes icl, tufA, kdsA, htpB, and acpXL, which encoded isocitrate lyase, elongation factor, 2-dehydro-3-deoxyphosphooctonate aldolase, heat shock protein, and acyl carrier protein, respectively. In addition, genomic islands (GIs) and phages/prophages were identified within the Brevundimonas genus. Importantly, a novel Brevundimonas species was identified from the feces of a patient (suffering from diarrhea) by the analyses of biochemical characteristics, phylogenetic tree of 16S rRNA gene, multilocus sequence analysis (MLSA) sequences, and genomic data. The name Brevundimonas pishanensis sp. nov. was proposed, with type strain CHPC 1.3453 (= GDMCC 1.2503T = KCTC 82824T). Brevundimonas spp. also showed obvious slow growth compared with that of Escherichia coli. Our study reveals insights into genomic characteristics and potential virulence-associated genes of Brevundimonas spp., and provides a basis for further intensive study of the pathogenicity of Brevundimonas. IMPORTANCEBrevundimonas spp., a group of bacteria from the family Caulobacteraceae, is associated with nosocomial infections, deserve widespread attention. Our study elucidated genes potentially associated with the pathogenicity of the Brevundimonas genus. We also described some new characteristics of Brevundimonas spp., such as small chromosome size, high G+C content, and slow-growth phenotypes, which made the Brevundimonas genus a good model organism for in-depth studies of growth rate traits. Apart from the comparative analysis of the genomic features of the Brevundimonas genus, we also reported a novel Brevundimonas species, Brevundimonas pishanensis, from the feces of a patient with diarrhea. Our study promotes the understanding of the pathogenicity characteristics of Brevundimonas species bacteria.