Innate Host Defense against &lt;b&gt;&lt;i&gt;Klebsiella pneumoniae&lt;/i&gt;&lt;/b&gt; and the Outlook for Development of Immunotherapies

Opoku‐Temeng, Clement; Małachowa, Natalia; Kobayashi, Scott D.; DeLeo, Frank R.

doi:10.1159/000518679

Cited by 16 publications

(10 citation statements)

References 193 publications

(246 reference statements)

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“…Capsule Polysaccharide (CPS) production is one of the most important virulence factors of bacteria, which is involved in resistance to complement-mediated killing and neutrophil-mediated phagocytosis [ 17 ]. Several studies indicated that change in CPS production also affects the susceptibilities of some antibiotics, such as polymyxin, carbapenem, and tigecycline [ 18–20 ].…”

Section: Introductionmentioning

confidence: 99%

Prevalence of hypervirulent and carbapenem-resistant Klebsiella pneumoniae under divergent evolutionary patterns

Tian

Liu

Chen

et al. 2022

Emerging Microbes & Infections

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K1/K2 hvKP strains acquire carbapenem-resistance plasmids, known as CR-hvKp, and carbapenem-resistant Klebsiella pneumoniae (CRKP) strains obtain virulence plasmids, recognized as hv-CRKP. The two different evolution patterns of hypervirulent combined carbapenem-resistant Klebsiella pneumoniae may lead to their different prevalence in hospitals. Our study aimed to investigate the prevalence of hv-CRKP and CR-hvKp strains and to analyze factors influencing their evolution and prevalence. We collected 890 K. pneumoniae genomes from GenBank and 530 clinical K. pneumoniae isolates from nine hospitals. Our study found that hv-CRKP strains were more prevalent than CR-hvKp strains and both were dominated by bla KPC-2 gene. The bla KPC-2 -carrying plasmids could mobilize non-conjugative virulence plasmids from hvKp strains to CRKP strains. The conserved oriT of virulence plasmids and the widespread of conjugative helper plasmids were potential factors for the mobilization of non-conjugative virulence plasmids. HvKp strains with KPC plasmid could hardly simultaneously exhibit hypervirulence and carbapenem resistance as CRKP strains with virulence plasmid, and we found that rfaH mutation reduced capsular synthesis and increased carbapenem resistance of the CR-hvKp strain. In summary, this study revealed that hv-CRKP strains were more suitable for survival in hospital settings than CR-hvKp strains and the widespread conjugative KPC-producing plasmids contributed to the emergence and prevalence of hv-CRKP strains.

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Section: Introductionmentioning

confidence: 99%

Prevalence of hypervirulent and carbapenem-resistant Klebsiella pneumoniae under divergent evolutionary patterns

Tian

Liu

Chen

et al. 2022

Emerging Microbes & Infections

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“…As K. pneumoniae is a typical extracellular bacterium, the effect of cellular immunity on K. pneumoniae is relatively limited (Opoku-Temeng et al, 2022). Lee et al found that T-helper (T H ) lymphocytes played a prominent role in the defense of K. pneumoniae through secreting cytokines such as IL-17 and IFN-g (Lee et al, 2015).…”

Section: T Cell-mediated Immune Responsementioning

confidence: 99%

“…It is known that innate immunity and adaptive immunity are equally crucial in resisting pathogen invasion, the adaptive immune response is slower and more specific. Another prominent feature for adaptive immunity is the production of immunologic memory which is activated rapidly during reinfection, resulting in protective response ( Bonilla and Oettgen, 2010 ; Opoku-Temeng et al., 2022 ). Adaptive immunity includes T cell-mediated cellular response and B cell-mediated humoral response ( Bonilla and Oettgen, 2010 ).…”

Section: Adaptive Immune Response To K Pneumoniaementioning

confidence: 99%

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Host defense against the infection of Klebsiella pneumoniae: New strategy to kill the bacterium in the era of antibiotics?

Liang

Wang²,

Lai³

et al. 2022

Front. Cell. Infect. Microbiol.

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Klebsiella pneumoniae (K. pneumoniae) is a typical gram-negative iatrogenic bacterium that often causes bacteremia, pneumonia and urinary tract infection particularly among those with low immunity. Although antibiotics is the cornerstone of anti-infections, the clinical efficacy of β-lactamase and carbapenems drugs has been weakened due to the emergence of drug-resistant K. pneumoniae. Recent studies have demonstrated that host defense plays a critical role in killing K. pneumoniae. Here, we summarize our current understanding of host immunity mechanisms against K. pneumoniae, including mechanical barrier, innate immune cells, cellular immunity and humoral immunity, providing a theoretical basis and the new strategy for the clinical treatment of K. pneumoniae through improving host immunity.

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“…K. pneumoniae has evolved into two pathotypes: classical and hypervirulent (hvKp) [4]. The classical K. pneumoniae is the leading cause of opportunistic healthcare-associated infections, such as urinary tract infections, pneumonia, wound and surgical site infections, and bacteraemia [5].…”

Section: Introductionmentioning

confidence: 99%

A New Live Auxotrophic Vaccine Induces Cross-Protection against Klebsiella pneumoniae Infections in Mice

et al. 2022

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The development of a whole-cell vaccine from bacteria auxotrophic for D-amino acids present in the bacterial cell wall is considered a promising strategy for providing protection against bacterial infections. Here, we constructed a prototype vaccine, consisting of a glutamate racemase-deficient mutant, for preventing Klebsiella pneumoniae infections. The deletion mutant lacks the murI gene and requires exogenous addition of D-glutamate for growth. The results showed that the K. pneumoniae ΔmurI strain is attenuated and includes a favourable combination of antigens for inducing a robust immune response and conferring an adequate level of cross-protection against systemic infections caused by K. pneumoniae strains, including some hypervirulent serotypes with elevated production of capsule polysaccharide as well as multiresistant K. pneumoniae strains. The auxotroph also induced specific production of IL-17A and IFN-γ. The rapid elimination of the strain from the blood of mice without causing disease suggests a high level of safety for administration as a vaccine.

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Innate Host Defense against <b><i>Klebsiella pneumoniae</i></b> and the Outlook for Development of Immunotherapies

Cited by 16 publications

References 193 publications

Prevalence of hypervirulent and carbapenem-resistant Klebsiella pneumoniae under divergent evolutionary patterns

Prevalence of hypervirulent and carbapenem-resistant Klebsiella pneumoniae under divergent evolutionary patterns

Host defense against the infection of Klebsiella pneumoniae: New strategy to kill the bacterium in the era of antibiotics?

A New Live Auxotrophic Vaccine Induces Cross-Protection against Klebsiella pneumoniae Infections in Mice

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