Hypervirulent Klebsiella Research Articles

Genomic analysis and therapeutic efficacy evaluation of bacteriophage PK2420 for pneumonia caused by hypervirulent Klebsiella pneumoniae (K20 serotype).

Hypervirulent Klebsiella pneumoniae (hvKp) strains are increasingly recognized for their aggressive nature, which leads to severe clinical outcomes. The emergence of multidrug-resistant strains constitutes a substantial challenge for clinical management. Phage therapy offers a potential solution to the antibiotic resistance crisis. A multidrug-resistant hvKp strain, K2420 (K20 serotype), was used to isolate bacteriophages from hospital sewage. Phage morphology, biological properties, and genome characteristics were analyzed using transmission electron microscopy, plaque assays, and whole-genome sequencing. Therapeutic safety and efficacy were assessed in an acute pneumonia murine model induced by intratracheal injection of K2420. Assessment parameters included bacterial load, phage titer, body temperature, cytokine levels, histopathological findings, and other relevant indicators. Phage PK2420, a member of the Autographiviridae family and Przondovirus genus, was identified. It rapidly lyses K. pneumoniae (K20 serotype), inhibits biofilm formation, and exhibits a burst size of 37.4 plaque-forming units/cell. The phage is stable at temperatures ranging from 0°C to 40°C and pH values between 6 and 9. Its genome, 41,155 bp in length, contains 46 coding sequences. The phage has no genes associated with antibiotic resistance, virulence, or lysogeny. In vivo, PK2420 substantially reduced K. pneumoniae bacterial loads, improved survival rates, and alleviated pneumonia severity without observable side effects. Phage PK2420 exhibits lytic activity against K. pneumoniae both in vitro and in murine models, providing a promising and safe option for the treatment of hvKp infections.IMPORTANCEOur investigation provides insights into the interaction mechanism among hypervirulent Klebsiella pneumoniae (hvKp) (K20 serotype), phage, and the host in a mouse pneumonia model, offering a valuable reference for future research on phage pharmacokinetics. This study demonstrated that bacteriophage PK2420 exhibits promising biosafety and therapeutic efficacy against hvKp-induced pulmonary infections and dissemination in a murine model. These findings suggest that phage PK2420 may be a potential option for the clinical treatment of hvKp infections.

The Brief Case: A renal abscess caused by ST35-KL108, a strain of multidrug-resistant hypervirulent Klebsiella pneumoniae.

The Brief Case: A renal abscess caused by ST35-KL108, a strain of multidrug-resistant hypervirulent Klebsiella pneumoniae.

Detection of hypervirulent Klebsiella pneumoniae among clinical isolates from select infections using virulence gene markers

Objectives Hypervirulent Klebsiella pneumoniae (hvKp) is a distinct pathotype of K. pneumoniae associated with community-acquired infections, and it generally exhibits susceptibility to antimicrobial agents. The objective of the study was to identify hvKp and determine the antibiotic susceptibility profiles of these isolates. Materials and Methods A total of 150 K. pneumoniae isolates were obtained from community-acquired infections. All isolates were subjected to string test and antimicrobial susceptibility test using Kirby–Bauer disc diffusion. Final confirmation was done using polymerase chain reaction (PCR), targeting three hvKp-specific virulence genes (p rmpA, iucA, and peg344). Statistical analysis The associations between the string test and virulence genes were assessed using the Chi-square test. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the string test were calculated using PCR as the gold standard. Results Among the 150 isolates, 62 (41.3%) were identified as hvKp. Abscesses (29) and pneumonia (22) were the most common clinical conditions, with neck abscesses as the predominant site. Of the 62 hvKp isolates, only 44 were string test-positive. Surprisingly, 22 string test-positive isolates lacked these genes, while 18 string test-negative isolates carried virulence genes. The sensitivity, specificity, PPV, and NPV of the string test were 66.7%, 78.5%, 71%, and 75%, respectively. Three hvKp isolates were multidrug-resistant. Conclusions Accurate detection of hvKp is critical in clinical settings due to its association with severe community-acquired infections, including deep-seated abscesses and pneumonia. The string test lacks both sensitivity and specificity, making it unreliable for hvKp identification. Therefore, the detection of virulence genes remains the gold standard. Early and precise diagnosis is essential for guiding appropriate treatment, including targeted antibiotic therapy and necessary drainage procedures for abscesses. The presence of multidrug resistance in certain isolates is a cause for concern, necessitating strict infection control measures to prevent the spread of such strains.

Genome Characterization of Carbapenem-Resistant Hypervirulent Klebsiella pneumoniae Strains, Carrying Hybrid Resistance-Virulence IncHI1B/FIB Plasmids, Isolated from an Egyptian Pediatric ICU.

Despite the increased reporting of Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKp) in Egypt, there is a paucity of information regarding the molecular characteristics of such strains. Herein, we present the genome sequence of two CR-hvKp strains, K22 and K45, which were isolated from VAP (ventilator-associated-pneumonia) patients admitted to pediatric ICU at Assiut University Children's Hospital, Egypt. K22 and K45 isolates were subjected to antimicrobial susceptibility testing and whole-genome sequencing. Genomic analysis was performed to characterize each strain, determining their plasmids, antimicrobial resistance (AMR) genes, and virulence determinants. K22 possessed an extensive drug resistance phenotype (XDR), whilst K45 exhibited a multidrug resistance phenotype (MDR), with genome sequencing revealing the presence of a diverse array of AMR genes. Both strains were resistant to the carbapenem antibiotic imipenem, carrying the OXA-48 carbapenemase, with K22 additionally possessing an NDM-1 carbapenemase. Each strain was considered high-risk, with K22 and K45 respectively belonging to sequence types ST383 and ST14 and possessing virulence genes implicated in hypervirulence (e.g., iucABCD-iutA and rmpA). Importantly, both strains carried multiple plasmid replicons, including an AMR/virulence IncHI1B/FIB hybrid plasmid and MDR IncL/M plasmids. This report highlights the critical role of plasmids in the evolution of virulent K. pneumoniae strains and suggests the circulation of an IncHI1B/FIB hybrid plasmid, simultaneously disseminating AMR and hypervirulence, amongst K. pneumoniae strains within Assiut University Children's Hospital.

A Rare Case of Necrotizing Soft Tissue Infection Involving the Neck and Mediastinum Due to Hypervirulent Klebsiella Pneumoniae

A Rare Case of Necrotizing Soft Tissue Infection Involving the Neck and Mediastinum Due to Hypervirulent Klebsiella Pneumoniae

Prevalence of hypervirulent Klebsiella pneumoniae and application of the novel Klebsiella phage vB_KpnP_D39 for biocontrol of serotypes K1, K2, and K57 in prepared food-related samples.

Prevalence of hypervirulent Klebsiella pneumoniae and application of the novel Klebsiella phage vB_KpnP_D39 for biocontrol of serotypes K1, K2, and K57 in prepared food-related samples.

Essentiality of the virulence plasmid-encoded factors in disease pathogenesis of the major lineage of hypervirulent Klebsiella pneumoniae varies in different infection niches.

Essentiality of the virulence plasmid-encoded factors in disease pathogenesis of the major lineage of hypervirulent Klebsiella pneumoniae varies in different infection niches.

Molecular epidemiological analysis and research on resistance and virulence of carbapenem-resistant Klebsiella pneumoniae in a tertiary hospital from 2016 to 2023

PurposeCarbapenem-resistant Klebsiella pneumoniae (CRKP) represents a significant global threat due to its high prevalence rates and limited therapeutic options. The primary objective of this study was to investigate the clinical distribution and molecular epidemiology of CRKP collected between 2016 and 2023 from a tertiary care hospital in northern China.MethodsPolymerase chain reaction (PCR) assays were used to identify resistance and virulence genes, while various assessments, including the string test and biofilm formation analysis, assessed CRKP’s virulence. Multilocus sequence typing (MLST) and whole-genome sequencing were employed to elucidate strain classification and plasmid characteristics.ResultsThe study identified 100 unique CRKP strains, primarily isolated from neurosurgery and ICU, with sputum as the most common specimen type. The majority of strains harbored blaKPC−2 as the primary resistance mechanism. All CRKP strains harbored a minimum of four virulence genes, with entB, mrkD, fimH, and ybtS being most commonly detected across the isolates. Notably, 66 of 100 strains were classified as carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP). The prevailing sequence type (ST) observed was ST11, with serotype KL47 being most prevalent initially, subsequently supplanted by ST11-KL64. Specific strains harbored blaKPC−2 on IncFII-type plasmids, along with other resistance genes, such as blaTEM−1. KP635_PlasmidB harbors multiple antibiotic resistance genes, and the sequence identity and coverage between KP635_PlasmidA and the NTUH-K2044 virulence plasmid are 99%, which contributes to the formation of a highly virulent and multidrug-resistant strain in KP635.ConclusionThe emergence of high resistance and hypervirulence in CRKP requires vigilance, enhanced surveillance, and stringent infection control measures to limit its spread.

Evidence of hypervirulent carbapenem-resistant Klebsiella pneumoniae in cats with urinary affections and associated humans in Egypt

The emergence of hypervirulent and carbapenem-resistant Klebsiella pneumoniae poses a significant threat to the public health of both cats and their owners. Therefore, conducting molecular characterization and phylogenetic analysis of K. pneumoniae strains in both cats and humans in Egypt is crucial. 108 feline and 101 human urine samples were collected and subjected to routine microbiological isolation and molecular identification of K. pneumoniae. Subsequently, phenotypic antimicrobial sensitivity patterns and molecular identification of classical virulence, hypervirulence, and carbapenem resistance genes were examined. A total of 46 K. pneumoniae isolates were recovered, comprising 43.4% (23 out of 53) from diseased humans, 4.17% (2 out of 48) from healthy humans, 22.95% (14 out of 61) from diseased felines, and 14.89% (7 out of 47) from healthy felines. The detection rates for narrow drug-resistant (NDR), multidrug-resistant (MDR), extensively drug-resistant (XDR), and pan drug-resistant (PDR) strains were 41.30%, 54.35%, 2.17%, and 2.17%, respectively. The distribution rates for mrKD, entB, K2, Kfu, and MagA genes were 76.1%, 82.6%, 8.7%, 13.0%, and 0%, respectively. In addition, the distribution of hypervirulence genes was 41.3%, 36.9%, 13.0%, 10.9%, and 17.4% for iucA, iroB, Peg344, rmPA, and rmPA2, respectively, and 43.5%, 30.4%, 19.6%, and 52.2% for NDM, OXA-48, VIM, and KPC resistance genes, respectively. Phylogenetic analysis of the entB gene from four recovered strains revealed a relationship between feline strains and other human strains. In conclusion, this study focused on the molecular characterization and phylogenetic analysis of hypervirulent and carbapenem-resistant K. pneumoniae in companion cats and humans in Egypt.

A systematic review of hypervirulent Klebsiella pneumoniae research: bibliometric and topic modeling perspectives.

Hypervirulent Klebsiella pneumoniae (hvKP) is an emerging global health threat, exhibiting increased virulence and multidrug resistance compared to classic K. pneumoniae. Understanding the research landscape surrounding hvKP is crucial for developing effective control strategies. This study aimed to comprehensively analyze the global research trends in hvKP from 2013 to 2024 using bibliometric and topic modeling techniques. Data from 1,014 articles on hvKP, retrieved from the Web of Science Core Collection, were analyzed using Bibliometrix, CiteSpace, and VOSviewer to assess publication trends, collaborations, geographical distribution, and keyword co-occurrence. Latent Dirichlet Allocation (LDA) topic modeling was employed to identify key research themes. The analysis revealed a steadily increasing volume of hvKP research, with China and the United States as major contributors. Four primary research themes emerged: high virulence phenotypes and mechanisms; drug resistance and treatment strategies; genetic and molecular mechanisms; and epidemiological and transmission characteristics. Research hotspots included virulence mechanisms, drug resistance, genomic detection approaches, and epidemiological features. This bibliometric analysis provides a comprehensive overview of hvKP research, highlighting key trends and research gaps. The identified research hotspots inform future research directions and contribute to the development of effective strategies for combating hvKP infections. The increasing research volume underscores the urgent need for continued investigation into this significant public health threat.

New insights and perspectives on the virulence of hypervirulent Klebsiella pneumoniae.

Klebsiella pneumoniae, a Gram-negative bacterium, comprises strains with diverse virulence potentials, ranging from classical to hypervirulent variants. Understanding the genetic basis underlying the virulence disparities between hypervirulent (hvKp) and classical K. pneumoniae (cKp) strains is crucial. hvKp strains are characterized by hypermucoviscosity, attributed to the presence of specific virulence genes and the production of molecules that aid in their ability to survive, evade host immune defenses, and cause infection. In contrast, classical strains exhibit a broader array of antimicrobial resistance determinants, conferring resistance to multiple antibiotics. Although current definitions of hvKp incorporate clinical features, phenotypes, and genotypes, identifying hvKp strains in clinical settings remains challenging. Genomic studies have been pivotal and have helped to identify distinct genetic profiles in hvKp strains, including unique virulence plasmids and chromosomal variations, underscoring the genetic diversity within K. pneumoniae populations. This review examines the virulence and genetic determinants associated with hvKp. The presence of genes defining hypervirulence, alongside considerations of their utility as biomarkers and targets for therapeutic strategies, is discussed, while also providing insight into biofilm formation by hvKp and key questions that need urgent responses in understanding hvKp.

Carbapenem-resistant hypervirulent Klebsiella pneumoniae: where is it headed in the tug-of-war between virulence and resistance?

Carbapenem-resistant hypervirulent Klebsiella pneumoniae: where is it headed in the tug-of-war between virulence and resistance?

Activation of GPR35 by kynurenic acid inhibits IL-1β secretion in macrophages during CR-hvKP-induced pneumonia.

Activation of GPR35 by kynurenic acid inhibits IL-1β secretion in macrophages during CR-hvKP-induced pneumonia.

Revisiting therapeutic options against resistant klebsiella pneumoniae infection: Phage therapy is key.

Revisiting therapeutic options against resistant klebsiella pneumoniae infection: Phage therapy is key.

Molecular epidemiology and emergence of sequence type 25 hypervirulent Klebsiella pneumoniae in pigs in the Netherlands (2013-2020): a global comparative analysis with human and pig isolates.

Klebsiella pneumoniae (Kp), a ubiquitous pathogen found in diverse ecological niches, poses a threat to human and animal health. Hypervirulent Kp (hvKp) is concerning for its acquisition of virulence and antimicrobial resistance genes through plasmids. This study investigates hvKp as a cause of septicaemia in piglets in the Netherlands and examines the role of plasmids in virulence and host association. We collected 41 Kp isolates cultured from necropsies submitted from 15 different farms (2013-2020) and sequenced them using long-read sequencing. We identified sequence type (ST) 25 as the dominant Kp (67%, 10/15 farms) associated with septicaemia in pigs in the Netherlands. ST25 isolates displayed a hypervirulent profile, including the K2 hyper-capsule type and carried an iuc3 virulence plasmid. Further analysis revealed two ST25 clonal groups: CG25 and CG3804, a novel porcine clone. Multidrug resistance was identified in CG25 isolates from five pig farms. There was one colistin-resistant isolate carrying mcr-1 on a plasmid. Comparative genomic analysis was performed by including a large dataset of related publicly available Kp genomes from ST25 humans (n=230) and pigs (n=12) of all STs for phylogenetic and plasmid analysis. Pangenomic analysis revealed significantly higher iuc3 prevalence in global CG25 pig isolates (98%, 40/41) compared to humans (10%, 24/234) correlating with their enhanced virulence (scores 3-4 vs 0-1). The study highlights ST25 hvKp causing septicaemia in piglets in the Netherlands for the first time. Aerobactin lineage iuc3 on a plasmid is associated with infections in pigs and is responsible for an increased virulence score.

A step forward in the puzzling diagnosis of hypervirulent Klebsiella pneumoniae

A step forward in the puzzling diagnosis of hypervirulent Klebsiella pneumoniae

Prevalence, Risk Factors, and Clinical Outcomes of Hypervirulent Klebsiella pneumoniae Strains among Klebsiella pneumoniae Infections: A Systematic Review and Meta-analysis.

Hypervirulent Klebsiella pneumoniae (HvKp) is a virulent strain associated with invasive infections. While initially community-acquired, hospital-acquired HvKp (HA-HvKp) and carbapenem-resistant HvKp (CR-HvKp) are increasingly reported. This meta-analysis evaluates the prevalence, risk factors, and clinical outcomes associated with HvKp, including CR-HvKp and HA-HvKp, among Kp infections. A systematic search of PubMed, Scopus, Embase, and Cochrane Library was conducted until December 2024. Observational studies comparing HvKp vs classical Kp (cKp), CR-HvKp vs carbapenem-sensitive HvKp (CS-HvKp), and HA-HvKp vs community-acquired HvKp (CA-HvKp) were included. Quality was assessed using the Joanna Briggs Critical Appraisal Tool, and pooled prevalence and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Fifty studies with 6,663 participants were included. The HvKp prevalence was 33.0%, with most studies from Asia, predominantly China. Temporal analysis revealed an increase in HvKp prevalence (27.7% in 2006-2018 to 38.5% in 2019-2024). The CR-HvKp prevalence rose from 9.5% to 16.5% (2016-2024). The HA-HvKp prevalence increased from 25.9 to 47.1%. Key risk factors included diabetes mellitus (OR = 1.56), CA-Kp (OR = 2.59), and hypermucoviscous (HM)-phenotype (OR = 29.79). Complications included liver abscess (OR = 6.35), metastatic spread (OR = 4.74), meningitis (OR = 11.14), and septic shock (OR = 1.30). Mortality was higher in HvKp infections but not statistically significant (p = 0.219). HA-HvKp and immunosuppression were significant CR-HvKp risk factors, with CR-HvKp showing higher mortality. Diabetes mellitus, CA-Kp infections, and HM-phenotype are significant risk factors for HvKp. The rising prevalence of CR-HvKp and HA-HvKp highlights the need for early detection, infection control, and targeted treatment strategies. Nagendra D, Chaudhuri S, Gupta N, Shanbhag V, Eshwara VK, Rao S, et al. Prevalence, Risk Factors, and Clinical Outcomes of Hypervirulent Klebsiella pneumoniae Strains among Klebsiella pneumoniae Infections: A Systematic Review and Meta-analysis. Indian J Crit Care Med 2025;29(4):370-393.

Detection of morphological variants of colistin-resistant Klebsiella pneumoniae associated with sepsis in Kerala, India.

Infections caused by colistin resistant Klebsiella pneumoniae are a major global health challenge linked to high mortality rates worldwide. Increased incidence of hypervirulent and drug-resistant Klebsiella causing life-threatening infections in young healthy individuals and asymptomatic carriage in the community has been largely reported in the Asian-Pacific Rim. This study conducted a molecular analysis of two morphologically distinct variants of K. pneumoniae that caused bacteremia and sepsis in a patient. Colony morphology of the isolates was characterized in various growth media, and the morphological variants differed in their mucoviscosity. The isolates were found to be serotype K2 (highly associated with hypervirulent Klebsiella) by molecular serotyping using specific PCR primers. The multidrug-resistant nature of the colony variants was evaluated by antibiotic susceptibility testing and it was found to have a similar antibiogram pattern in in vitro. An increased minimum inhibitory concentration (MIC) of colistin (>64 μg mL-1) was detected in both isolates using broth microdilution, and they were found to be highly resistant to colistin. Molecular analysis revealed that the isolates possessed a chromosomal mutation in mgrB, which causes colistin resistance. The increased incidence of infection caused by colistin-resistant K. pneumoniae requires continuous monitoring, and appropriate measures are necessary to control its adaptive evolution in healthcare settings.

Multidrug-resistant hypervirulent Klebsiella pneumoniae: an evolving superbug.

Multidrug-resistant hypervirulent Klebsiella pneumoniae (MDR-hvKP) combines high pathogenicity with multidrug resistance to become a new superbug. MDR-hvKP reports continue to emerge, shattering the perception that hypervirulent K. pneumoniae (hvKP) strains are antibiotic sensitive. Patients infected with MDR-hvKP strains have been reported in Asia, particularly China. Although hvKP can acquire drug resistance genes, MDR-hvKP seems to be more easily transformed from classical K. pneumoniae (cKP), which has a strong gene uptake ability. To better understand the biology of MDR-hvKP, this review discusses the virulence factors, resistance mechanisms, formation pathways, and identification of MDR-hvKP. Given their destructive and transmissible potential, continued surveillance of these organisms and enhanced control measures should be prioritized.

Leveraging collateral sensitivity to counteract the evolution of bacteriophage resistance in bacteria.

The escalating antibiotic resistance crisis poses a major global health threat. Bacteriophage therapy offers a promising alternative for combating multidrug-resistant infections. However, bacterial resistance to phages remains a significant hurdle. Innovative strategies are needed to overcome this challenge. In this study, we developed a phage cocktail based on our phage library, consisting of three phages that suppressed phage resistance of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKp). This cocktail capitalized on dual instances of collateral sensitivity, thereby constraining the evolution of phage resistance. The first-layered collateral sensitivity arose from overlapping coverage between capsular polysaccharide (CPS) and lipopolysaccharide (LPS), rendering the bacteria resistant to CPS-binding phages but more susceptible to LPS-binding phages. The second-layered collateral sensitivity resulted from an O serotype switch (from O1 to O2), causing resistance to O1 antigen-binding phages but increasing susceptibility to phages that target the O2 antigen. This dual-layered collateral sensitivity phage cocktail effectively mitigated infection caused by CR-hvKp in mice. Our research highlights the importance of the collateral sensitivity mechanism in counteracting the evolution of phage resistance and offers a sophisticated strategy for configuring phage cocktails to eliminate bacterial resistance.