Inactivation of the virulence factors from 2,3-butanediol-producing Klebsiella pneumoniae

Abstract

The microbiological production of 2,3-butanediol (2,3-BDO) has attracted considerable attention as an alternative way to produce high-value chemicals from renewable sources. Among the number of 2,3-BDO-producing microorganisms, Klebsiella pneumoniae has been studied most extensively and is known to produce large quantity of 2,3-BDO from a range of substrates. On the other hand, the pathogenic characteristics of the bacteria have limited its industrial applications. In this study, two major virulence traits, outer core LPS and fimbriae, were removed through homologous recombination from 2,3-BDO-producing K. pneumoniae 2242 to expand its uses to the industrial scale. The K. pneumoniae 2242 ∆wabG mutant strain was found to have an impaired capsule, which significantly reduced its ability to bind to the mucous layer and evade the phagocytic activity of macrophage. The association with the human ileocecal epithelial cell, HCT-8, and the bladder epithelial cell, T-24, was also reduced dramatically in the K. pneumoniae 2242 ∆fimA mutant strain that was devoid of fimbriae. However, the growth rate and production yield for 2,3-BDO were unaffected. The K. pneumoniae strains developed in this study, which are devoid of the major virulence factors, have a high potential for the efficient and sustainable production of 2,3-BDO.

Klebsiella pneumoniae: Going on the Offense with a Strong Defense

“…It has important roles in protecting against complement, including preventing C1q binding to bacteria, which inhibits subsequent activation of the complement pathway, as well as binding C3b away from the outer bacterial membrane and, thus, abrogating bacterial lysis by the complement membrane attack complex. jority of reports stating that wabG is harbored by 88 to 100% of K. pneumoniae isolates, although one report found wabG in only 5.3% of isolates (268,(270)(271)(272)(273)(274). K. pneumoniae strains lacking this gene are unable to generate the LPS outer core or to retain capsular antigen and are attenuated in intraperitoneal, pneumonic, and UTI rodent models of infection (275).…”

Identification of Pathogenic Factors in Klebsiella pneumoniae Using Impedimetric Sensor Equipped with Biomimetic Surfaces

“…The fimbriae of K. pneumoniae have been reported to be an important adhesion factor as they attach to a specific carbohydrate moiety on the host cell’s surface [17,31]. The fimbriae form a specific interaction with mannosyl residues of N-linked glycoprotein on the outer layer of target cells, which suggests that the fimbriae of K. pneumoniae play a critical role in early stage of infection [32].…”

“…K. pneumoniae KCTC 2242 ∆ wabG mutant strain and K. pneumoniae KCTC 2242 ∆ fimA mutant strain were constructed by Jung et al [21] and Huynh et al [17]. For complementation studies, the wabG and fimA genes were cloned into pBBR1MCS5 vector (CABRI Consortium, Genova, Italy) as follows.…”

“…Herein, we describe an impedimetric sensor equipped with a functionalized electrode, which mimics the surfaces of epithelial cells and the luminal surfaces of epithelial organs, and its use to identify the virulence factors of K. pneumoniae associated with the adhesion process during the early stage of infection. Outer-core LPS and fimbriae of K. pneumoniae are major virulence factors and are known to be responsible for its adhesion to the mucous layer and epithelial cells, respectively [17,18]. The mucins, which are major components of mucous layers, compose a family of glycoproteins that cover the luminal surfaces of epithelial organs [19].…”

Formate and Nitrate Utilization in Enterobacter aerogenes for Semi‐Anaerobic Production of Isobutanol

“…Therefore, E. aerogenes is considered to be a highly useful strain for isobutanol production. Although there is a concern about the pathogenicity of Enterobacteriaceae family bacteria including E. aerogenes , removal of lipopolysaccharide protein (WabG) or fimbriae protein (FimA) have been proved to alleviate its pathogenic feature …”