Citrobacter freundii fitness during bloodstream infection

Abstract

Sepsis resulting from microbial colonization of the bloodstream is a serious health concern associated with high mortality rates. The objective of this study was to define the physiologic requirements of Citrobacter freundii in the bloodstream as a model for bacteremia caused by opportunistic Gram-negative pathogens. A genetic screen in a murine host identified 177 genes that contributed significantly to fitness, the majority of which were broadly classified as having metabolic or cellular maintenance functions. Among the pathways examined, the Tat protein secretion system conferred the single largest fitness contribution during competition infections and a putative Tat-secreted protein, SufI, was also identified as a fitness factor. Additional work was focused on identifying relevant metabolic pathways for bacteria in the bloodstream environment. Mutations that eliminated the use of glucose or mannitol as carbon sources in vitro resulted in loss of fitness in the murine model and similar results were obtained upon disruption of the cysteine biosynthetic pathway. Finally, the conservation of identified fitness factors was compared within a cohort of Citrobacter bloodstream isolates and between Citrobacter and Serratia marcescens, the results of which suggest the presence of conserved strategies for bacterial survival and replication in the bloodstream environment.

Expression of a Shiga-Like Toxin during Plastic Colonization by Two Multidrug-Resistant Bacteria, Aeromonas hydrophila RIT668 and Citrobacter freundii RIT669, Isolated from Endangered Turtles (Clemmys guttata)

“…It is found in soil, water, food and as a commensal in the gastrointestinal tract of humans and other animals [56,57,59]. However, it is increasingly a nosocomial and environmental pathogen, causing pneumonia, diarrhea, urinary tract and bloodstream infections [59][60][61][62][63][64][65][66]. Food poisoning cases caused by C. freundii isolates have been reported [59,62].…”

The Tat system and its dependent cell division proteins are critical for virulence of extra-intestinal pathogenic Escherichia coli

“…In Y. pseudotuberculosis, several Tat substrates are identified critical to cause systematic infection, among which ΔsufI shows the largest attenuation [35]. In Citrobacter freundii, it has also been shown that sufI mutation results in a very significant in vivo fitness defect [15]. A recent study in S. Typhimurium demonstrates that the deletion of the two Tat-dependent amidase encoding genes leads to significant in vivo fitness attenuation, mainly due to cell division defect especially in the inflamed gut where stress conditions including high osmolarity and antimicrobial peptides are present [18].…”

“…Due to the diversity of Tat substrate proteins, Tat system disruption causes pleiotropic defects, affecting bacterial growth, cell division, motility, biofilm formation, iron acquisition, stress response, etc [9,10]. Moreover, the crucial role of the Tat system in pathogenesis has been reported in several important bacterial pathogens, including Pseudomonas aeruginosa [11], E. coli O157 [12], Salmonella enterica serovar Typhimurium [13,14], Citrobacter freundii [15], and Yersinia pseudotuberculosis [16]. Efforts have been made by several research groups to unravel how the Tat system affects bacterial virulence.…”

Antibiotics susceptibility patterns of Citrobacter freundii isolated from pa-tients with urinary tract infection in Al-Najaf governorate – Iraq

“…Citrobacter freundii (C. freundii) is a gram-negative bacterium, motile, oxidase negative and non-capsulated (Lakhundi et al, 2017;Liu et al, 2018). Citrobacter freundii is one of the most important gram-negative bacteria cause urinary tract infection and other diseases in human such as bacteremia (Park et al, 2013;Ouyang et al, 2018;Anderson et al, 2018). Recently, Citrobacter freundii isolated from hospitals patients with urinary tract infection becomes more resistant to different antibiotics like beta-lactamase, 3rd generation cephalosporins and aminoglycosides (Aljanaby and Gafil 2013; Castanheira et al, 2018;Akinbami et al, 2018).…”