Klebsiella pneumoniae: adaptive immune landscapes and vaccine horizons

Wantuch, Paeton L.; Rosen, David A.

doi:10.1016/j.it.2023.08.005

Cited by 17 publications

(5 citation statements)

References 142 publications

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“…ST147NDM-1 has been classified as a pandrug-resistant and hypervirulent strain 26 which has not only been responsible for local outbreaks in Italy [19][20][21] but has been causative of infections worldwide 20,[52][53][54] . Additionally, genomic surveillance reports indicate that KL64, associated with enhanced virulence 67 , is replacing some previously prevalent capsular loci through intraspecies clone shifting 68 and became the third emerging capsule type for hypervirulent strains after K1 and K2 serotypes 4,69 . Indeed, carbapenem-resistant KL64-expressing ST11 Kp represents the most common AMR lineage in China 70 .…”

Section: Discussionmentioning

confidence: 99%

“…Among AMR pathogens, Enterobacteriaceae causing threats in hospital settings are considered the most critical 2 and are currently dominated by Klebsiella pneumoniae (Kp) species 3 . Most Kp strains that cause severe infections belong to two major pathotypes, namely the classical and hypervirulent ones 4 . Classical Kp is a frequent cause of healthcare-associated infections and can easily acquire mobile genetic elements associated with AMR 5 .…”

Section: Introductionmentioning

confidence: 99%

“…Although valuable, the above findings find little applicability to ST147 NDM-1 for one major reason: the astonishing variability of antigenic polysaccharidic structures across Kp strains. Indeed, more than 100 capsule serotypes (K antigen) have been described so far 37 , while 11 distinct O-antigen serogroups exist, with four O-antigens (O1, O2, O3, and O5) associated with 80-90% of Kp clinical isolates 4 . Moreover, continuous diversification of O-antigen structures, such as addition of pyruvate to O1b 38 and GlcNAc to O2ac 39 , generates new epitopes.…”

Section: Introductionmentioning

confidence: 99%

“…NDMs are encoded by blaNDM genes located on large multi-resistance plasmids that have been spreading across highrisk AMR Kp clones throughout all continents 7,8 . On the other hand, hypervirulent Kp (hvKp) isolates carry large virulence plasmids encoding genes related to capsule synthesis and siderophore production 4 . Despite showing higher susceptibility to antimicrobial agents, hvKp strains can cause severe community-acquired infections, such as pyogenic liver abscess, endophthalmitis, and meningitis [7][8][9][10] , even in healthy individuals.…”

Section: Introductionmentioning

confidence: 99%

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Anti-capsule human monoclonal antibodies protect against hypervirulent and pandrug-resistantKlebsiella pneumoniae

Roscioli,

Galli Fonseca,

Bosch

et al. 2024

Preprint

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SUMMARYThe silent pandemic caused by antimicrobial resistance (AMR) requires innovative therapeutic approaches. Human monoclonal antibodies (mAbs), which are among the most transformative, safe and effective drugs in oncology and autoimmunity, are rarely used for infectious diseases and not yet used for AMR. Here we applied an antigen-agnostic strategy to isolate extremely potent human mAbs againstKlebsiella pneumoniae(Kp) sequence type 147 (ST147), a hypervirulent and pandrug-resistant clonotype which is spreading globally. Isolated mAbs target the bacterial capsule and the O-antigen. Surprisingly, although both capsule- and O-antigen-specific mAbs displayed bactericidal activity in the picomolar rangein vitro, only the capsule-specific mAbs were protective against fulminant ST147 bloodstream infection. Protection correlated within vitrobacterial uptake by macrophages and enchained bacterial growth. Our study describes the only drug able to protect against pandrug-resistant Kp and provides a strategy to isolate mAbs and identify correlates of protection against AMR bacteria.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Anti-capsule human monoclonal antibodies protect against hypervirulent and pandrug-resistantKlebsiella pneumoniae

Roscioli,

Galli Fonseca,

Bosch

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…About 10 monoclonal antibodies are in clinical trials, of which three have been approved for marketing. 60 Despite the encouraging progress in the development of vaccines, the diversity of K. pneumoniae strains presents significant challenges that need to be overcome to create effective vaccines. Ongoing research is essential to find effective vaccines that offer protection, especially against this increasingly resistant pathogen.…”

Section: Immunotherapymentioning

confidence: 99%

Mechanisms of Antibiotic Resistance and Developments in Therapeutic Strategies to Combat Klebsiella pneumoniae Infection

Li,

Kumar,

Zhang

2024

IDR

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Infections with drug-resistant bacteria have become one of the greatest public health challenges, and K. pneumoniae is among the top six drug-resistant bacteria. K. pneumoniae often causes nosocomial infections, leading to illnesses such as pneumonia, liver abscesses, soft tissue infections, urinary tract infections, bacteremia, and in some cases death. As the pathogen continues to evolve and its multidrug resistance increases, K. pneumoniae poses a direct threat to humans. Drug resistance in K. pneumoniae may occur due to the formation of biofilms, efflux pumps, and the production of β-lactamases. In many cases, resistance is further enhanced by enzymatic modification and loss of porins. Drug resistance to K. pneumoniae has led to a decline in the effectiveness of conventional therapies against this pathogen. Therefore, there is an urgent need to accelerate the development of new antibiotics and explore new therapeutic approaches such as antimicrobial peptides, phages, traditional Chinese medicine, immunotherapy, Antimicrobial nanoparticle technology, antisense oligonucleotides and gene editing technologies. In this review, we discuss the mechanisms of drug resistance in K. pneumoniae and compare several new potential therapeutic strategies to overcome drug resistance in the treatment of K. pneumoniae infections.

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Phosphate‐Containing Glycolipids: A Review on Synthesis and Bioactivity

Pinheiro,

Freitas,

Branco

2024

ChemMedChem

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Phosphate‐containing glycolipids (PcGL) are scarcer than the better understood glycolipids. They are composed of arrangements of phosphate, carbohydrates and glycerol units and are always found associated with lipids. PcGL are often found associated with cell membranes, meaning their roles concern cell interactions. This article aims to provide an up‐to‐date overview of the existing knowledge and research on PcGL, emphasizing their synthesis and wide range of biological activities. When it comes to the synthesis of PcGL compounds, the strategies for glycosylation mainly rely on the thioglycoside donor, the trichloroacetmaidate donor and halide donor strategies, while phosphorylation is stapled and falls on either phosphite chemistry or phosphoryl chloride chemistry. Certain bacteria utilize PcGLs in their pathogenicity, triggering an inflammatory response within the host's defense mechanisms. The best‐known examples of these structures are teichoic acids, lipopolysaccharide and the capsular polysaccharide found in bacteria, all of which are frequently implicated in bacterial infections. Given the degree of variability within PcGL structures, they were found to display a wide range of bioactivities. PcGL compounds were found to: (1) have anti‐metastatic properties, (2) behave as agonists or antagonists of platelet aggregation, (3) be mostly pro‐inflammatory, (4) display antifungal and antibiotic activity and (5) have neurogenic activity.

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Klebsiella pneumoniae: adaptive immune landscapes and vaccine horizons

Cited by 17 publications

References 142 publications

Anti-capsule human monoclonal antibodies protect against hypervirulent and pandrug-resistantKlebsiella pneumoniae

Anti-capsule human monoclonal antibodies protect against hypervirulent and pandrug-resistantKlebsiella pneumoniae

Mechanisms of Antibiotic Resistance and Developments in Therapeutic Strategies to Combat Klebsiella pneumoniae Infection

Phosphate‐Containing Glycolipids: A Review on Synthesis and Bioactivity

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