Virulence Determinants of Colistin-Resistant K. pneumoniae High-Risk Clones
by
, , , , and
Ozlem Dogan
1, 
Cansel Vatansever
1,
Nazli Atac
1,
Ozgur Albayrak
1,
Sercin Karahuseyinoglu
2,
Ozgun Ekin Sahin
3,
Bilge Kaan Kilicoglu
3,
Atalay Demiray
3,
Onder Ergonul
1, 
Mehmet Gönen
4 and
Fusun Can
1,* 1
Department of Infectious Diseases and Clinical Microbiology, School of Medicine, Koc University, Istanbul 34450, Turkey
2
Department of Histology and Embryology, School of Medicine, Koc University, Istanbul 34450, Turkey
3
School of Medicine, Koc University, Istanbul 34450, Turkey
4
Department of Industrial Engineering, College of Engineering, Koc University, Istanbul 34450, Turkey
*
Author to whom correspondence should be addressed.
Biology 2021, 10(5), 436; https://doi.org/10.3390/biology10050436
Submission received: 26 March 2021
/
Revised: 5 May 2021
/
Accepted: 6 May 2021
/
Published: 14 May 2021
(This article belongs to the Special Issue Microbial Diversity and Microbial Resistance)
Simple Summary
The iron uptake systems are associated with virulence in colistin-resistant high-risk clones of K. pneumoniae. The isolates belonging to high-risk clones of K. pneumoniae are resistant to phagocytosis by neutrophils and induce NET formation.
Abstract
We proposed the hypothesis that high-risk clones of colistin-resistant K. pneumoniae (ColR-Kp) possesses a high number of virulence factors and has enhanced survival capacity against the neutrophil activity. We studied virulence genes of ColR-Kp isolates and neutrophil response in 142 patients with invasive ColR-Kp infections. The ST101 and ST395 ColR-Kp infections had higher 30-day mortality (58%, p = 0.005 and 75%, p = 0.003). The presence of yersiniabactin biosynthesis gene (ybtS) and ferric uptake operon associated gene (kfu) were significantly higher in ST101 (99%, p ≤ 0.001) and ST395 (94%, p < 0.012). Being in ICU (OR: 7.9; CI: 1.43–55.98; p = 0.024), kfu (OR:27.0; CI: 5.67–179.65; p < 0.001) and ST101 (OR: 17.2; CI: 2.45–350.40; p = 0.01) were found to be predictors of 30-day mortality. Even the neutrophil uptake of kfu+-ybtS+ ColR-Kp was significantly higher than kfu--ybtS- ColR-Kp (phagocytosis rate: 78% vs. 65%, p < 0.001), and the kfu+-ybtS+ ColR-Kp survived more than kfu--ybtS- ColR-Kp (median survival index: 7.90 vs. 4.22; p = 0.001). The kfu+-ybtS+ ColR-Kp stimulated excessive NET formation. Iron uptake systems in high-risk clones of colistin-resistant K. pneumoniae enhance the success of survival against the neutrophil phagocytic defense and stimulate excessive NET formation. The drugs targeted to iron uptake systems would be a promising approach for the treatment of colistin-resistant high-risk clones of K. pneumoniae infections.
Keywords:
colistin resistance; K. pneumoniae; iron uptake; net formation; phagocytosis
