In SilicoIdentification of Three Types of Integrative and Conjugative Elements (ICEs) inElizabethkingia anophelisStrains Isolated from Around the World

Abstract

27Elizabethkingia anophelis is an emerging global multidrug-resistant opportunistic pathogen. 28 We assessed the diversity among 13 complete genomes and 23 draft genomes of E. anophelis 29 derived from various environmental settings and human infections from different geographic 30 regions around the world over past decades from 1950s. Thirty-one of these 36 strains harbor 31 integrative and conjugative elements (ICEs). A total of 52 ICEs were identified, and 32 categorized into three ICE types based on the architecture of signature genes in the 33 conjugation module. The type II and III ICEs were found to integrate into regions adjacent to 34 tRNA genes, while type I ICEs used a variety of integration sites, inserting into intergenic 35 regions or even directly into a gene, sometimes disrupting gene function. Integrases such as 36 tyrosine recombinases, serine recombinases and DDE transposases were found in most ICEs. 37 The ICEs carry various cargo genes including transcription regulators and those involved in 38 antibiotic resistance. The CRISPR-Cas system was found in nine strains, including four 39 strains in which CRISPR-Cas machinery and ICEs co-exist. ICE distribution in the strains 40 showed no geographic or temporal patterns. The ICEs in E. anophelis differ in gene structure 41 and sequence from CTnDOT, a well-studied ICE prevalent in Bacteroides spp. This is the 42 first set of ICEs identified in the family Flavobacteriaceae. As a prevalent type of mobile 43 genetic elements in various strains of E. anophelis around the world, the categorization of 44 ICEs will facilitate further investigations such as virulence, genome epidemiology and 45 adaptation genomics of E. anophelis. 46 Importance 47Elizabethkingia anophelis is an opportunistic human pathogen, and the genetic diversity 48 between strains from around the world becomes apparent as more genomes are sequenced. 49The Integrative Conjugative Element (ICE), found in many bacterial species, contains genes 50 3 for transfer via conjugation and integration into the chromosome, along with various cargo 51 genes. ICEs are identified in 31 of 36 strains and categorized into three types based on 52 architecture of modular genes, integrases, and integration sites. ICE distribution in different 53 strains displays no spatial and temporal patterns. Several ICE-containing strains also 54 possessed CRISPR-Cas units, considered to be the bacterial adaptive immune system 55 providing protection against phage and predatory mobile genetic elements. This co-existence 56 suggests that ICEs are beneficial or at least not harmful to the bacterial cells they inhabit. 57ICEs as a component of the mobile genetic repertoire enable recipients to resist antibiotics, 58 survive disinfecting agents, and adapt to various ecological niches.

The antibiotic resistance and pathogenicity of a multidrug‐resistant Elizabethkingia anophelis isolate

“…This transposon element inserted into and disrupted the gene MutY (an adenine DNA glycosylase that is required for fixing G‐A mis‐pairs), making the strain more liable to mutation and outbreak infection (Perrin et al, ). Recent research showed that ICEs were ubiquitous in E. anophelis species; 31 of selected 36 E. anophelis strains (86%) harbored 32 ICEs (Xu, Pei, Nicholson, Lan, & Xia, ). These ICEs were classified into three types: ICEEaI, ICEEaII, and ICEEaIII.…”

“…For example, conjugative elements ICEEaII and ICEEaIII were identified in the Singapore outbreak strain NUHP1. Also, the Anopheles mosquito strains Ag1 and R26 contained ICEEaIII (Xu et al, ). More detailed analysis of ICEs will clarify pathogenesis and drug resistance mechanisms of E. anophelis .…”