Siderophores: More than Stealing Iron

Behnsen, Judith; Raffatellu, Manuela

doi:10.1128/mbio.01906-16

Cited by 65 publications

(53 citation statements)

References 17 publications

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“…The ability of a bacterium to secrete more than one type of siderophore enhances its ability to colonize the GIT and prevent neutralization of one siderophore by the host. The most prevalent siderophore secreted by K. pneumoniae is enterobactin due to its high affinity for iron …”

Section: Pathogenic Mechanisms and Virulence Factors Of K Pneumoniae Imentioning

confidence: 99%

“…The most prevalent siderophore secreted by K. pneumoniae is enterobactin due to its high affinity for iron. 50,51 Another component of K. pneumoniae virulence is the lipopolysaccharide (LPS), an endotoxin responsible for protecting the bacteria against host humoral defenses. 52 It is comprised of an O antigen, a core oligosaccharide and lipid A.…”

Section: Pathogenic Mechanisms and Virulence Factors Of K Pneumoniae Imentioning

confidence: 99%

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Impact of Klebsiella pneumoniae in lower gastrointestinal tract diseases

Kaur

Vadivelu

Samudi

2018

J of Digest Diseases

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The 2016 Global Burden of Disease report by WHO revealed that diseases of the gastrointestinal tract (GIT) had one of the highest incidence rates worldwide. The plethora of factors that contribute to the development of GIT-related illnesses can be divided into genetic, environmental and lifestyle factors. Apart from that, the role that infectious agents play in the development of GIT diseases has piqued the interest of researchers worldwide. The human gut harbors approximately 10 bacteria in it with increasing concentration toward the lower GIT. Among the various microbiota that colonize the human gut, Gram-negative bacteria have been most notoriously linked to GIT-related diseases such as inflammatory bowel disease (IBD) including Crohn's disease and ulcerative colitis and colorectal cancer (CRC). Some of the notable culprits that have been attributed to these diseases are Bacteroides fragilis, Fusobacterium nucleatum, Escherichia coli and Helicobacter pylori. However, studies in recent years are beginning to recognize a new player, Klebsiella pneumoniae (K. pneumoniae) in the causation and progression of GIT diseases. Once synonymous with infections and diseases of the upper respiratory tract, K. pneumoniae has now emerged as one of the pathogens commonly isolated from patients with GIT diseases. However, extensive studies attributing K. pneumoniae to GIT diseases, particularly that of CRC are scanty. Therefore, this review intends to shed light on the association of K. pneumoniae in gastrointestinal diseases such as Crohn's disease, ulcerative colitis as well as CRC.

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Section: Pathogenic Mechanisms and Virulence Factors Of K Pneumoniae Imentioning

confidence: 99%

Section: Pathogenic Mechanisms and Virulence Factors Of K Pneumoniae Imentioning

confidence: 99%

Impact of Klebsiella pneumoniae in lower gastrointestinal tract diseases

Kaur

Vadivelu

Samudi

2018

J of Digest Diseases

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“…More than 70% of the reference genes were detected in at least one K. aerogenes isolate (Supplementary table 7). Virulence factors shared by all isolates included the fimA-K operon, involved in adherence to human mucosal or epithelial surfaces [42]; ent , fep and iro , which encode enterobactin and salmochelin siderophores [43, 44]; rcsAB , regulators of mucoid phenotype A [45], among others (Supplementary table 7). We also found intrinsic genes encoding toxins related to K. aerogenes physiology during infection, such as colibactin (ClbD), enterotoxin (SenB) and microcin (MceG and MceH), which could be explored as novel drug targets.…”

Section: Resultsmentioning

confidence: 99%

Genomic analysis unveils important aspects of population structure, virulence, and antimicrobial resistance inKlebsiella aerogenes

Passarelli‐Araujo

Palmeiro

Moharana

et al. 2019

Preprint

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Klebsiella aerogenes is an important pathogen in healthcare‐associated infections. Nevertheless, in comparison to other clinically important pathogens, K. aerogenes population structure, genetic diversity, and pathogenicity remain poorly understood. Here, we elucidate K. aerogenes clonal complexes (CCs) and genomic features associated with resistance and virulence. We present a detailed description of the population structure of K. aerogenes based on 97 publicly available genomes by using both multilocus sequence typing and single‐nucleotide polymorphisms extracted from the core genome. We also assessed virulence and resistance profiles using Virulence Finder Database and Comprehensive Antibiotic Resistance Database, respectively. We show that K. aerogenes has an open pangenome and a large effective population size, which account for its high genomic diversity and support that negative selection prevents fixation of most deleterious alleles. The population is structured in at least 10 CCs, including two novel ones identified here, CC9 and CC10. The repertoires of resistance genes comprise a high number of antibiotic efflux proteins as well as narrow‐ and extended‐spectrum β‐lactamases. Regarding the population structure, we identified two clusters based on virulence profiles because of the presence of the toxin‐encoding clb operon and the siderophore production genes, irp and ybt. Notably, CC3 comprises the majority of K. aerogenes isolates associated with hospital outbreaks, emphasizing the importance of constant monitoring of this pathogen. Collectively, our results may provide a foundation for the development of new therapeutic and surveillance strategies worldwide.

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“…These genes were found to be associated with 30-day mortality. Yersiniabactin type siderophore is encoded in high pathogenicity island which is responsible for high mortality and dissemination of infections (20, 21). It was also reported to be associated with pulmonary infections (3, 22).…”

Section: Discussionmentioning

confidence: 99%

“…Another important disease strategy of hypervirulent clones is immune evasion from the innate response (24). The interaction of siderophores with host cells promotes pathogenicity of K.pneumoniae by induction of proinflammatory cytokines (21). Proinflammatory cytokines have a protective effect against K.pneumoniae by recruitment of neutrophils to the infection site.…”

Section: Discussionmentioning

confidence: 99%

The role of iron uptake systems in the pathogenesis of colistin-resistant hypervirulent K.pneumoniae infections

Doğan

Vatansever

Ataç

et al. 2019

Preprint

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16Here we proposed the hypothesis that hypervirulent colistin resistant K.pneumoniae (ColR-Kp) exhibit 17 high number of virulence factors and have enhanced survival capacity against neutrophil activity. 18We studied virulence genes of ColR-Kp isolates and neutrophil response in 142 patients with invasive 19 infections. 20The patients infected with hypervirulent ST101 and ST395 ColR-Kp had higher 30-day mortality (58%, 21 p=0.005 and 75%, p=0.003, respectively. The yersiniabactin biosynthesis gene (ybtS) and ferric uptake 22 operon associated gene (kfu) were significantly higher in ST101 (99%, p=<0.001) and in ST395 23 (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) 24 and ST101 (OR: 17.2; CI: 2.45-350.40; p=0.01) were found to be predictors of 30-day mortality. The 25 uptake of kfu + -ybtS + ColR-Kp by neutrophils was significantly higher than kfu --ybtS -ColR-Kp (78% vs 26 65%, p<0.001). However, kfu + -ybtS + ColR-Kp were more resistant to the killing activity of neutrophils 27 than negative ones (7.90 vs 4.22; p=0.001). The kfu + -ybtS + ColR-Kp stimulated excessive NET formation 28 while the NET's against kfu --ybtS -ColR-Kp were weak and rare. 29Iron uptake systems enhance successful survival of K.pneumoniae against neutrophil phagocytic 30 defense, and stimulate excessive NET formation. The drugs targeted to iron uptake systems would be 31 a promising approach for treatment of hypervirulent K.pneumoniae infections. 32 33 34 35 39 40 41 65 diseases, type of infection, isolation site, blood biochemical parameters, predisposing factors such as 66 having operation within last one month, intensive care unit admission (ICU), type of antimicrobial 67 agents used for empirical and agent-specific therapy, duration of colistin therapy before isolation of 68 colistin-resistant isolates, and carbapenem resistance was used. The patients were followed up for 157 13.13) vs 4.22 (range:0.36-5.64), respectively (p=0.001). The survival index of S.epidermidis and 158 K.pneumoniae controls were 0.64 and 1.89, respectively (Figure2). The survival index of two ybtSkfu + 159isolates were 12.04 and 12.13, and it was 5.13 in one ybtS + kfuisolate. 161Among 21 isolates, four was in ST101 clone. The median phagocytosis rate 80% was found to be and 162 the survival index was 8.51. 164After NETosis, the mean colony count of two kfu + -ybtS + isolates was 5.50X10 6 and it was 4.05x10 6 for 165 kfu --ybtSstrains. The colony count of ATCC K.pneumoniae was 4.3x10 6 . Confocal microscopy study 166 showed that the kfu + -ybtS + isolate stimulated abundant NET formation with excessive release of 167 chromatin granular content to the extracellular area. However, the NET's against kfu --ybtSnegative 168 ColR-Kp were weak and seen only in few areas (Figure 3). 169 170 Discussion 171 ColR-HvKP infections are usually fatal because of limited therapeutic options due to extensive drug 172 resistance and successful immune escape mechanisms of these pathogens. Alternative approaches are

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Siderophores: More than Stealing Iron

Cited by 65 publications

References 17 publications

Impact of Klebsiella pneumoniae in lower gastrointestinal tract diseases

Impact of Klebsiella pneumoniae in lower gastrointestinal tract diseases

Genomic analysis unveils important aspects of population structure, virulence, and antimicrobial resistance inKlebsiella aerogenes

The role of iron uptake systems in the pathogenesis of colistin-resistant hypervirulent K.pneumoniae infections

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