Predicting class switch recombination in B-cells from antibody repertoire data.

Statistical and machine learning methods have proved useful in many areas of immunology. In this paper, we address for the first time the problem of predicting the occurrence of class switch recombination (CSR) in B-cells, a problem of interest in understanding antibody response under immunological challenges. We propose a framework to analyze antibody repertoire data, based on clonal (CG) group representation in a way that allows us to predict CSR events using CG level features as input. We assess and compare the performance of several predicting models (logistic regression, LASSO logistic regression, random forest, and support vector machine) in carrying out this task. The proposed approach can obtain an unweighted average recall of 71 % $71\%$ with models based on variable region descriptors and measures of CG diversity during an immune challenge and, most notably, before an immune challenge.

Characterization of uropathogenic E. coli O25b-B2-ST131, O15:K52:H1, and CGA: Neutrophils apoptosis, serum bactericidal assay, biofilm formation, and virulence typing.

Pathogenic and drug-resistant strains of Escherichia coli (E. coli) O25b-B2-ST131, O15:H1-D-ST393, and CGA (clonal group A) clonal groups have spread worldwide. This study aimed at determining E. coli epidemic clonal groups, their virulence factors, biofilm formation, neutrophils apoptosis, and antimicrobial resistance pattern of uropathogenic E. coli. A total of 95 CTX-M-1-producing E. coli clinical isolates were enrolled. E. coli O25b-B2-ST131, CGA, and O15:K52:H1 were identified by serotyping and phylogrouping and allele-specific polymerase chain reaction-based assay. Antibiotic susceptibility, biofilm formation, hemolysis, and human serum bactericidal assay were performed. Neutrophil apoptosis was assayed by flow cytometry. Nine E. coli clonal groups including six O25b-B2-ST131 strains, two CGA, and one O15:K52:H1-D-ST393 strains were detected. One O25b-B2-ST131 isolate was a strong biofilm-producer. Three ST131 isolates had type I fimbriae. Furthermore, all the CGA and O15:K52:H1 and three of ST131 isolates harbored the P fimbriae. The virulence genes ompT, fimH, and traT were detected among all the clonal groups. The apoptosis was induced by O25b-B2-ST131, CGA, and O15:K52:H1 E. coli. There was no significant difference regarding apoptosis induction among clonal groups. Furthermore, the presence of the cdt, usp, and vat genes was significantly associated with the apoptosis of neutrophils by O25b-B2-ST131, CGA, and O15:K52:H1-D-ST393 clonal groups.

Epidemiological Investigation of Hospital Transmission of Corynebacterium striatum Infection by Core Genome Multilocus Sequence Typing Approach.

Corynebacterium striatum has recently received increasing attention due to its multiple antimicrobial resistances and its role as an invasive infection/outbreak agent. Recently, whole-genome sequencing (WGS)-based core genome multilocus sequence typing (cgMLST) has been used in epidemiological studies of specific human pathogens. However, this method has not been reported in studies of C. striatum. In this work, we aim to propose a cgMLST scheme for C. striatum. All publicly available C. striatum genomes, 30 C. striatum strains isolated from the same hospital, and 1 epidemiologically unrelated outgroup C. striatum strain were used to establish a cgMLST scheme targeting 1,795 genes (hereinafter referred to as 1,795-cgMLST). The genotyping results of cgMLST showed good congruence with core genome-based single-nucleotide polymorphism typing in terms of tree topology. In addition, the cgMLST provided a greater discrimination than the MLST method based on 6 housekeeping genes (gyrA, gyrB, hsp65, rpoB, secA1, and sodA). We established a clonal group (CG) threshold based on 104 allelic differences; a total of 56 CGs were identified from among 263 C. striatum strains. We also defined an outbreak threshold based on seven allelic differences that is capable of identifying closely related isolates that could give clues on hospital transmission. According to the results of analysis of drug-resistant genes and virulence genes, we identified CG4, CG5, CG26, CG28, and CG55 as potentially hypervirulent and multidrug-resistant CGs of C. striatum. This study provides valuable genomic epidemiological data on the diversity, resistance, and virulence profiles of this potentially pathogenic microorganism. IMPORTANCE Recently, WGS of many human and animal pathogens has been successfully used to investigate microbial outbreaks. The cgMLST schema are powerful genotyping tools that can be used to investigate potential epidemics and provide classification of the strains precise and reliable. In this study, we proposed the development of a cgMLST typing scheme for C. striatum, and then we evaluated this scheme for its applicability to hospital transmission investigations. This report describes the first cgMLST schema for C. striatum. The analysis of hospital transmission of C. striatum based on cgMLST methods has important clinical epidemiological significance for improving nosocomial infection monitoring of C. striatum and in-depth understanding of its nosocomial transmission routes.

Salmonella Derby from pig production chain over a 10-year period: antimicrobial resistance, biofilm formation, and genetic relatedness.

The aim of this study was to evaluate 140 Salmonella Derby isolates collected over a 10-year period from porcine origins (environment, pig carcass, lymph nodes, intestinal content, and pork) for their phenotypic and genotypic antimicrobial resistance, their ability to produce biofilm, and their genetic relatedness. The minimum inhibitory concentration (MIC) was determined using microdilution broth method and antimicrobial resistance genes were investigated by PCR. The quantification of biofilm formation was performed in sterile polystyrene microtiter plates. Genetic relatedness was determined by Xba-I macrorestriction analysis. The highest frequencies of non-wildtype (nWT) populations were observed against tetracycline (75.7%), streptomycin (70%), and colistin (11.4%), whereas wildtype populations were observed against ciprofloxacin, ceftazidime, and gentamicin. The resistance genes found were blaTEM (ampicillin), aadA variant (streptomycin/spectinomycin), tetA (tetracycline), and floR (florfenicol). On 96-well polystyrene microtiter plate, 68.6% of the isolates proved to be biofilm producers. Among 36 S. Derby isolates selected to PFGE analysis, 22 were clustered with 83.6% of similarity. Additionally, 27 isolates were clustered in 11 pulsotypes, which presented more than one strain with 100% of similarity. Most of S. Derby isolates were able to form biofilm and were classified as nWT or resistant to tetracycline, streptomycin, and colistin. PFGE allowed the identification of closely related S. Derby isolates that circulated in pig slaughterhouses and pork derived products along a decade.

Temporal and Racial Differences Associated with Atopic Dermatitis Staphylococcusaureus and Encoded Virulence Factors.

Atopic dermatitis (AD) is an inflammatory skin condition strongly associated with Staphylococcus aureus colonization and infection. S. aureus strains shift in populations in ~10-year intervals depending on virulence factors. Shifts in S. aureus virulence factors may in part explain the racial differences observed in the levels of prevalence and severity of AD. AD S. aureus isolates collected from 2011 to 2014 (103 isolates) and in 2008 (100 isolates) were examined for the prevalence of genes encoding superantigens (SAgs). The strains from 2011 to 2014 were obtained from AD patients as a part of the National Institute of Allergy and Infectious Diseases (NIAID) Atopic Dermatitis Research Network (ADRN). The prevalence of SAg genes was investigated temporally and racially. The enterotoxin gene cluster (EGC) was more prevalent in the 2011-2014 AD isolates than in the 2008 AD isolates. The prevalences of virulence factor genes were similar in European American (EA) and Mexican American (MA) patients but differed in 6 of 22 SAg genes between EA and African American (AA) or MA and AA isolates; notably, AA isolates lacked tstH, the gene encoding toxic shock syndrome toxin 1 (TSST-1). The presence of tstH and sel-p (enterotoxin-like P) was associated with decreased clinical severity and increased blood eosinophils, respectively. The EGC is becoming more prevalent, consistent with the previously observed 10 years of cycling of S. aureus strains. Race-specific S. aureus selection may account for differences in virulence factor profiles. The lack of TSST-1-positive (TSST-1+) AD S. aureus in AA is consistent with the lack of AAs acquiring TSST-1-associated menstrual toxic shock syndrome (TSS). IMPORTANCE Monitoring pathogen emergence provides insight into how pathogens adapt in the human population. Secreted virulence factors, important contributors to infections, may differ in a manner dependent on the strain and host. Temporal changes of Staphylococcus aureus toxigenic potential, for example, in encoding toxic shock syndrome toxin 1 (TSST-1), contributed to an epidemic of TSS with significant health impact. This study monitored changes in atopic dermatitis (AD) S. aureus isolates and demonstrated both temporal and host infection differences according to host race based on secreted superantigen potential. The current temporal increase in enterotoxin gene cluster superantigen prevalence and lack of the gene encoding TSST-1 in AAs predict differences in infection types and presentations.