Aerobactin Mediates Virulence and Accounts for Increased Siderophore Production under Iron-Limiting Conditions by Hypervirulent (Hypermucoviscous) Klebsiella pneumoniae

Russo, Thomas A.; Olson, Ruth; MacDonald, Ulrike; Metzger, Daniel; Maltese, Lauren M.; Drake, Eric J.; Gulick, Andrew M.

doi:10.1128/iai.01667-13

Cited by 232 publications

(237 citation statements)

References 55 publications

(69 reference statements)

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“…Moreover, in Shigella flexneri, combined deletion of iucD and ferrous iron acquisition systems (feoB and/or sitA) leads to smaller plaque formation on Henle cell monolayers (65). A recent study also demonstrated that deletion of iucA in hypervirulent Klebsiella pneumoniae leads to less growth in human ascites fluid and to less virulence in mice (66).…”

Section: Discussionmentioning

confidence: 99%

The Small RNA RyhB Contributes to Siderophore Production and Virulence of Uropathogenic Escherichia coli

et al. 2014

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eIn Escherichia coli, the small regulatory noncoding RNA (sRNA) RyhB and the global ferric uptake regulator (Fur) mediate iron acquisition and storage control. Iron is both essential and potentially toxic for most living organisms, making the precise maintenance of iron homeostasis necessary for survival. While the roles of these regulators in iron homeostasis have been well studied in a nonpathogenic E. coli strain, their impact on the production of virulence-associated factors is still unknown for a pathogenic E. coli strain. We thus investigated the roles of RyhB and Fur in iron homeostasis and virulence of the uropathogenic E. coli (UPEC) strain CFT073. In a murine model of urinary tract infection (UTI), deletion of fur alone did not attenuate virulence, whereas a ⌬ryhB mutant and a ⌬fur ⌬ryhB double mutant showed significantly reduced bladder colonization. The ⌬fur mutant was more sensitive to oxidative stress and produced more of the siderophores enterobactin, salmochelins, and aerobactin than the wild-type strain. In contrast, while RyhB was not implicated in oxidative stress resistance, the ⌬ryhB mutant produced lower levels of siderophores. This decrease was correlated with the downregulation of shiA (encoding a transporter of shikimate, a precursor of enterobactin and salmochelin biosynthesis) and iucD (involved in aerobactin biosynthesis) in this mutant grown in minimal medium or in human urine. iucD was also downregulated in bladders infected with the ⌬ryhB mutant compared to those infected with the wild-type strain. Our results thus demonstrate that the sRNA RyhB is involved in production of iron acquisition systems and colonization of the urinary tract by pathogenic E. coli.

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Section: Discussionmentioning

confidence: 99%

The Small RNA RyhB Contributes to Siderophore Production and Virulence of Uropathogenic Escherichia coli

et al. 2014

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“…When considering these infections, it is important to recall that HV strains are far more likely to cause community-acquired and systemic infections in otherwise healthy individuals, but for the most part, these strains are geographically limited to Taiwan and Southeast Asia. In contrast, classical strains of K. pneumoniae typically cause serious nosocomial infections or UTIs and can be found worldwide (41,(48)(49)(50). While there is a broad overlap of the types of infections caused by classical versus HV strains, some diseases are far more likely to be caused by HV than classical strains.…”

Section: Infections Caused By K Pneumoniaementioning

confidence: 99%

“…Interestingly, while aerobactin is found only rarely in classical strains causing lung infection, it may be the predominant siderophore expressed in certain HV K. pneumoniae strains causing lung infection (331). HV K. pneumoniae strains have an increased ability to acquire iron through amplified siderophore production, and aerobactin makes up the vast majority of the total siderophores produced in at least one HV K. pneumoniae strain (49). Furthermore, one study found that aerobactin, but not enterobactin, yersiniabactin, or salmochelin, is needed for successful infection by HV K. pneumoniae in pneumonic and subcutaneous mouse infection models (49,331).…”

Section: Figmentioning

confidence: 99%

“…HV K. pneumoniae strains have an increased ability to acquire iron through amplified siderophore production, and aerobactin makes up the vast majority of the total siderophores produced in at least one HV K. pneumoniae strain (49). Furthermore, one study found that aerobactin, but not enterobactin, yersiniabactin, or salmochelin, is needed for successful infection by HV K. pneumoniae in pneumonic and subcutaneous mouse infection models (49,331). In a mouse model of intraperitoneal HV K. pneumoniae infection, aerobactin plays a functionally redundant role with yersiniabactin and salmochelin, where only the simultaneous deletion of all three siderophores attenuates the strain in vivo (319).…”

Section: Figmentioning

confidence: 99%

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Klebsiella pneumoniae: Going on the Offense with a Strong Defense

Paczosa

Mecsas

2016

Microbiol Mol Biol Rev

1,366

1,345

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SUMMARYKlebsiella pneumoniaecauses a wide range of infections, including pneumonias, urinary tract infections, bacteremias, and liver abscesses. Historically,K. pneumoniaehas caused serious infection primarily in immunocompromised individuals, but the recent emergence and spread of hypervirulent strains have broadened the number of people susceptible to infections to include those who are healthy and immunosufficient. Furthermore,K. pneumoniaestrains have become increasingly resistant to antibiotics, rendering infection by these strains very challenging to treat. The emergence of hypervirulent and antibiotic-resistant strains has driven a number of recent studies. Work has described the worldwide spread of one drug-resistant strain and a host defense axis, interleukin-17 (IL-17), that is important for controlling infection. Four factors, capsule, lipopolysaccharide, fimbriae, and siderophores, have been well studied and are important for virulence in at least one infection model. Several other factors have been less well characterized but are also important in at least one infection model. However, there is a significant amount of heterogeneity inK. pneumoniaestrains, and not every factor plays the same critical role in all virulentKlebsiellastrains. Recent studies have identified additionalK. pneumoniaevirulence factors and led to more insights about factors important for the growth of this pathogen at a variety of tissue sites. Many of these genes encode proteins that function in metabolism and the regulation of transcription. However, much work is left to be done in characterizing these newly discovered factors, understanding how infections differ between healthy and immunocompromised patients, and identifying attractive bacterial or host targets for treating these infections.

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“…2,10,11 Construction of in-frame deletion mutants in Serotype K20 and CPS gene exchange from serotype K1 to K20…”

Section: Detection Of Virulence Determinants For Hypervirulent Strainmentioning

confidence: 99%

Effect in virulence of switching conserved homologous capsular polysaccharide genes fromKlebsiella pneumoniaeserotype K1 into K20

et al. 2016

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The capsular polysaccharides in different serotypes of Klebsiella pneumoniae (KP) coded by the (CPS) gene cluster are characterized by a conserved and a hyper-variable region. We performed a virulence study by switching genes in the highly conserved region of the CPS cluster between strains. Six genes in the CPS conserved region in serotype K20, including galF, acidPPc, wzi, wza, wzb and wzc, were knocked out and replaced by the homologous genes from serotype K1. Compared to the parental K20 strain, the mutants showed a decline in lethality (LD 50 ) in mice from 10-fold to > 10 5 -fold and were categorized in terms of the effect on virulence as low (L) for galF and acidPPC, moderate (M) for wzi, and high (H) for wza, wzb and wzc. Although substituting the acidPPC gene from K1 for acidPPC in the K20 strain fully restored virulence, substitution with the wzi, wza, wzb or wzc homologs from K1 did not. The restoration with wzi from K1 led to a partial restoration of virulence, with the LD 50 in mice changing from 10 4 to 10 3 CFU . For the wza, wzb and wzc genes, Complementation of K20 wza, wzb and wzc from K1 resulted in varied degrees of lethality in mice. Variable improvement in serum killing and phagocytosis was observed when the knockout mutants were compared with the geneswitched strains. In conclusion, homologous genes for capsule synthesis failed to exhibit the same functionality when switched between serotypes and virulence was decreased in different degree in according to the genes' homology.

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Aerobactin Mediates Virulence and Accounts for Increased Siderophore Production under Iron-Limiting Conditions by Hypervirulent (Hypermucoviscous) Klebsiella pneumoniae

Cited by 232 publications

References 55 publications

The Small RNA RyhB Contributes to Siderophore Production and Virulence of Uropathogenic Escherichia coli

The Small RNA RyhB Contributes to Siderophore Production and Virulence of Uropathogenic Escherichia coli

Klebsiella pneumoniae: Going on the Offense with a Strong Defense

Effect in virulence of switching conserved homologous capsular polysaccharide genes fromKlebsiella pneumoniaeserotype K1 into K20

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