Comparative analysis of virulence determinants, phylogroups, and antibiotic susceptibility patterns of typical versus atypical Enteroaggregative E. coli in India

Abstract

Enteroaggregative Escherichia coli (EAEC) is an evolving enteric pathogen that causes acute and chronic diarrhea in developed and industrialized nations in children. EAEC epidemiology and the importance of atypical EAEC (aEAEC) isolation in childhood diarrhea are not well documented in the Indian setting. A comparative analysis was undertaken to evaluate virulence, phylogeny, and antibiotic sensitivity among typical tEAEC versus aEAEC. A total of 171 EAEC isolates were extracted from a broad surveillance sample of diarrheal (N = 1210) and healthy children (N = 550) across North India. Polymerase chain reaction (PCR) for the aggR gene (master regulator gene) was conducted to differentiate tEAEC and aEAEC. For 21 virulence genes, we used multiplex PCR to classify possible virulence factors among these strains. Phylogenetic classes were identified by a multiplex PCR for chuA, yjaA, and a cryptic DNA fragment, TspE4C2. Antibiotic susceptibility was conducted by the disc diffusion method as per CLSI guidelines. EAEC was associated with moderate to severe diarrhea in children. The prevalence of EAEC infection (11.4%) was higher than any other DEC group (p = 0.002). tEAEC occurrence in the diarrheal group was higher than in the control group (p = 0.0001). tEAEC strain harbored more virulence genes than aEAEC. astA, aap, and aggR genes were most frequently found in the EAEC from the diarrheal population. Within tEAEC, this gene combination was present in more than 50% of strains. Also, 75.8% of EAEC strains were multidrug-resistant (MDR). Phylogroup D (43.9%) and B1 (39.4%) were most prevalent in the diarrheal and control group, respectively. Genetic analysis revealed EAEC variability; the comparison of tEAEC and aEAEC allowed us to better understand the EAEC virulence repertoire. Further microbiological and epidemiological research is required to examine the pathogenicity of not only typical but also atypical EAEC.

The Biology and the Evolutionary Dynamics of Diarrheagenic Escherichia coli Pathotypes

“…All strains in lineage 1 were O166:H15 and belonged to ST349, lineage 2 consisted of serogroups O44, O73, and O17/O77 in combination with either H18 or H34 and ST130, while lineage 3 carried O153:H30 serotype and ST38 [146]. Contrarily, in India, EAEC strains implicated in diarrhea were more prevalent in phylogroup D [158] suggesting that the diversity in the pathotype is not limited by geography. While EAEC subtypes are believed to differ in their virulence determinants content, this hypothesis and comparative phylogenetic analysis of aEAEC and tEAEC are underexplored.…”

Real-time multiplex PCR assay reveals the increased prevalence of Campylobacter spp and diarrhoeagenic Escherichia coli in humans from Vellore, South India

“…Nearly 40 % of diarrhoeal episodes among children <5 years of age are caused by members of the DEC pathotype in low-to middle-income countries [25]. On the basis of their specific virulence determinant, phenotypic traits and clinical symptoms, DEC strains are classified into six major pathotypes, this includes enteropathogenic E. coli (EPEC), enterotoxigenic E. coli (ETEC), enteroaggregative E. coli (EAEC), enteroinvasive E. coli (EIEC), enterohemorrhagic E. coli (EHEC), and diffusely adherent E. coli (DAEC) [22,[26][27][28].…”

A Novel Adult Murine Model of Typical Enteroaggregative Escherichia coli Infection Reveals Microbiota Dysbiosis, Mucus Secretion, and AAF/II-Mediated Expression and Localization of β-Catenin and Expression of MUC1 in Ileum

“…Enteroaggregative Escherichia coli (EAEC) is one of the six diarrheagenic E. coli pathotypes ( Harrington et al., 2006 ; Estrada-Garcia and Navarro-Garcia, 2012 ; Modgil et al., 2020 ). EAEC strain’s defining phenotype is the aggregative adherence pattern on epithelial cells, attributable to the aggregative adherence fimbriae (AAF) ( Estrada-Garcia and Navarro-Garcia, 2012 ; Modgil et al., 2020 ).…”

“…Enteroaggregative Escherichia coli (EAEC) is one of the six diarrheagenic E. coli pathotypes ( Harrington et al., 2006 ; Estrada-Garcia and Navarro-Garcia, 2012 ; Modgil et al., 2020 ). EAEC strain’s defining phenotype is the aggregative adherence pattern on epithelial cells, attributable to the aggregative adherence fimbriae (AAF) ( Estrada-Garcia and Navarro-Garcia, 2012 ; Modgil et al., 2020 ). The AggR regulon, which defines typical EAEC (tEAEC) strains, was first described in the archetype EAEC strain 042 (serotype O44:H18) isolated from a Peruvian child with diarrhea ( Czeczulin et al., 1997 ; Harrington et al., 2006 ).…”

“…tEAEC infection causes enteric disease in diverse clinical settings, including acute diarrheal illness, particularly in infants and young children from less developed regions of the world ( Estrada-Garcia and Navarro-Garcia, 2012 ; Patzi-Vargas et al., 2015 ; Modgil et al., 2020 ), and severe diarrhea among Peruvian infants and adults infected with HIV ( Garcia et al., 2010 ; Medina et al., 2010 ), and is the second most common cause of traveler’s diarrhea worldwide ( Paredes-paredes et al., 2011 ; Jensen et al., 2014 ). In patients, EAEC causes watery mucoid diarrhea, which may contain fecal leukocytes and/or lactoferrin and can be especially severe among infants and adult travelers ( Jiang et al., 2003 ; Acosta et al., 2016 ; Meza-segura et al., 2020 ).…”