Protein Malnutrition Facilitates Intestinal Colonization with Highly Resistant Klebsiella pneumoniae

Area of Science:

• Microbiology
• Immunology
• Pediatrics

Background:

• Highly Resistant Enterobacterales (HRE) infections disproportionately affect children in low- and middle-income countries with high malnutrition rates.
• Mechanisms linking malnutrition to HRE colonization in pediatric populations remain unclear.

Purpose of the Study:

• To investigate the link between pediatric malnutrition and intestinal colonization by carbapenem-resistant Klebsiella pneumoniae (CR-Kp).
• To identify mechanisms underlying malnutrition-associated susceptibility to HRE.

Main Methods:

• Development of a pediatric malnutrition mouse model using a protein-deficient (PD) diet.
• Intestinal colonization experiments with clinical CR-Kp isolates in PD-fed and control diet (CD) mice.
• Assessment of CR-Kp burden, transmission, and impact of antibiotic treatment; analysis of secondary bile acid levels.

Main Results:

• PD-fed mice exhibited significantly higher CR-Kp colonization (3-4 log increase) and persistent colonization for up to 6 weeks compared to CD-fed mice.
• CR-Kp transmission occurred between PD-fed but not CD-fed cage mates.
• Reduced secondary bile acids in PD-fed and antibiotic-treated mice correlated inversely with CR-Kp burden; secondary bile acids inhibited CR-Kp growth in vitro.

Conclusions:

• Pediatric malnutrition enhances susceptibility to intestinal colonization by CR-Kp in a mouse model.
• Nutrition-dependent colonization resistance appears to rely on an intact gut microbiota.
• Reduced secondary bile acids may be a critical factor mediating malnutrition-induced susceptibility to HRE colonization.