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1.
Int Microbiol ; 2024 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-38252202

RESUMEN

Hypervirulent Klebsiella pneumoniae (hvKp) is an emerging pathogen and causes endophthalmitis, liver abscess, osteomyelitis, meningitis, and necrotizing soft tissue infections in both immunodeficient and healthy people. The acquisition of the antibiotic resistance genes of hvKp has become an emerging concern throughout the globe. In this study, a total of 74 K. pneumoniae isolates were collected and identified by VITEK2 and blaSHV gene amplification. Out of these, 18.91% (14/74) isolates were identified as hvKp by both phenotypic string test and genotypic iucA PCR amplification. The antibiotic susceptibility revealed that 57.14% (8/14) isolates were multidrug-resistant (MDR) and 35.71% (5/14) isolates were extremely drug-resistant (XDR). All the isolates were resistant to ß-lactam, ß-lactamase + inhibitor groups of antibiotics, and the least resistance to colistin. Of 14 hvKp isolates, all isolates are positive for iroB (100%), followed by iutA (92.85%), peg344 (85.71%), rmpA (57.14%), and magA (21.42%) genes. Among serotypes, K1 was the most prevalent serotype 21.4% (3/14), followed by K5 14.3% (2/14). The most common carbapenemase gene was blaOXA-48 (78.57%) followed by blaNDM (14.28%) and blaKPC (14.28%) which co-carried multiple resistance genes such as blaSHV (100%), blaCTX-M (92.85%), and blaTEM (78.57%). About 92.85% (13/14) of hvKp isolates were strong biofilm producers, while one isolate (hvKp 10) was the only moderate biofilm producer. The (GTG)5-PCR molecular typing method revealed high diversity among the hvKp isolates in the tertiary care hospital. Our findings suggest that MDR-hvKp is an emerging pathogen and a challenge for clinical practice. In order to avoid hvKp strain outbreaks in hospital settings, robust infection control and effective surveillance should be implemented.

2.
Acta Microbiol Immunol Hung ; 71(1): 52-60, 2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38289372

RESUMEN

Hypervirulent Klebsiella pneumoniae is an emerging pathogen that has gained attention due to its increased ability to cause infections even in healthy individuals. The aim of this study is to investigate virulence factors in K. pneumoniae strains isolated from clinical specimens and their association with carbapenem resistance. The study was conducted on 260 isolates identified between 2018 and 2023 at the Mohammed V Military Teaching Hospital in Rabat, Morocco. The isolates were categorized based on their susceptibility to antibiotics. The hypermucoviscosity was determined by a string test, while the presence of capsular serotypes and virulence genes were identified by PCR. Among our strains, 6.2% (n = 16) exhibited hypervirulent characteristics, 56% were resistant to carbapenem. Notably, 5.7% (n = 6) of carbapenem-resistant isolates expressed the hypermucoviscous phenotype, while 1.5% (n = 2) of carbapenem-susceptible K. pneumoniae isolates exhibited the same trait. In our study, we found that a total of 10 isolates (3.8%) had virulent capsular serotypes, with K2 being the most prevalent 40% (n = 4) and K20 in 30% (n = 3). Furthermore, we detected the presence of the Aerobactin gene in 1.5% (n = 4) of the isolates examined. Based on our findings, it appears that there was no correlation between the presence of virulence factors and carbapenem resistance. In conclusion, identifying hypervirulent K. pneumoniae in clinical specimens and assessing their antibiotic resistance profiles are crucial to ensure effective therapy and to prevent outbreaks.


Asunto(s)
Carbapenémicos , Infecciones por Klebsiella , Humanos , Carbapenémicos/farmacología , Klebsiella pneumoniae , Infecciones por Klebsiella/epidemiología , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Factores de Virulencia/genética
3.
Int J Mol Sci ; 25(3)2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38339222

RESUMEN

Hypervirulent Klebsiella pneumoniae (hvKp) is a variant that has been increasingly linked to severe, life-threatening infections including pyogenic liver abscess and bloodstream infections. HvKps belonging to the capsular serotypes K1 and K2 have been reported worldwide, however, very scarce studies are available on their genomics and virulence. In the current study, we report four hypermucoviscous extended-spectrum ß-lactamase-producing hvKp clinical strains of capsular serotype K1 and K2 isolated from pus and urine of critically ill patients in tertiary care hospitals in Oman. These strains belong to diverse sequence types (STs), namely ST-23(K1), ST-231(K2), ST-881(K2), and ST-14(K2). To study their virulence, a Galleria mellonella model and resistance to human serum killing were used. The G. mellonella model revealed that the K1/ST-23 isolate was the most virulent, as 50% of the larvae died in the first day, followed by isolate K2/ST-231 and K2/ST-14, for which 75% and 50% of the larvae died in the second day, respectively. Resistance to human serum killing showed there was complete inhibition of bacterial growth of all four isolates by the end of the first hour and up to the third hour. Whole genome sequencing (WGS) revealed that hvKp strains display a unique genetic arrangement of k-loci. Whole-genome single-nucleotide polymorphism-based phylogenetic analysis revealed that these hvKp isolates were phylogenetically distinct, belonging to diverse clades, and belonged to different STs in comparison to global isolates. For ST-23(K1), ST-231(K2), ST-881(K2), and ST-14(K2), there was a gradual decrease in the number of colonies up to the second to third hour, which indicates neutralization of bacterial cells by the serum components. However, this was followed by a sudden increase of bacterial growth, indicating possible resistance of bacteria against human serum bactericidal activity. This is the first report from Oman detailing the WGS of hvKp clinical isolates and assessing their resistance and virulence genomics, which reinforce our understanding of their epidemiology and dissemination in clinical settings.


Asunto(s)
Klebsiella pneumoniae , Factores de Virulencia , Humanos , Serogrupo , Filogenia , Virulencia/genética , Factores de Virulencia/genética , Antibacterianos/farmacología , Antibacterianos/uso terapéutico
4.
Arch Microbiol ; 204(4): 202, 2022 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-35244778

RESUMEN

Klebsiella pneumoniae is an opportunistic pathogen that can cause several infections, mainly in hospitalised or immunocompromised individuals. The spread of K. pneumoniae emerging virulent and multidrug-resistant clones is a worldwide concern and its identification is crucial to control these strains especially in hospitals. This article reports data related to multi-resistant K. pneumoniae strains, isolated from inpatients in the city of Manaus, Brazil, harbouring virulence and antimicrobial-resistance genes, including high-risk international clones belonging to clonal group (CG) 258. Twenty-one strains isolated from different patients admitted to four hospitals in the city of Manaus, located in the state of Amazonas, Northern Brazil (Amazon Rainforest region) were evaluated. The majority of strains (61.9% n = 13) were classified as multidrug-resistant (MDR), and five strains (23.8%) as extensively drug-resistant (XDR). Several virulence and antimicrobial-resistance genes were found among the strains and eight strains (38.1%) presented the hyper-mucoviscous phenotype. MLST analysis demonstrated a great diversity of STs among the strains, totaling 12 different STs (ST11, ST23, ST198, ST277, ST307, ST340, ST378, ST462, ST502, ST3991, ST3993 and ST5209). Three of these (ST11, ST23 and ST340) belong to CG258.


Asunto(s)
Infecciones por Klebsiella , Klebsiella pneumoniae , Antibacterianos/farmacología , Brasil/epidemiología , Farmacorresistencia Bacteriana Múltiple/genética , Humanos , Infecciones por Klebsiella/epidemiología , Pruebas de Sensibilidad Microbiana , Tipificación de Secuencias Multilocus , Estudios Retrospectivos , beta-Lactamasas/genética
5.
Int J Mol Sci ; 23(13)2022 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-35806365

RESUMEN

In recent years, an increase in the prevalence hypermucoviscous carbapenem-resistant Klebsiella pneumoniae with sequence type 25 (ST25) was detected in hospitals of Tucuman (Northwest Argentina). In this work, the virulence and the innate immune response to two K. pneumoniae ST25 strains (LABACER 01 and LABACER 27) were evaluated in a murine model after a respiratory challenge. In addition, comparative genomics was performed with K. pneumoniae LABACER01 and LABACER27 to analyze genes associated with virulence. Both LABACER01 and LABACER27 were detected in the lungs of infected mice two days after the nasal challenge, with LABACER01 counts significantly higher than those of LABACER27. Only LABACER01 was detected in hemocultures. Lactate dehydrogenase (LDH) and albumin levels in bronchoalveolar lavage (BAL) samples were significantly higher in mice challenged with LABACER01 than in LABACER27-infected animals, indicating greater lung tissue damage. Both strains increased the levels of neutrophils, macrophages, TNF-α, IL-1ß, IL-6, KC, MCP-1, IFN-γ, and IL-17 in the respiratory tract and blood, with the effect of LABACER01 more marked than that of LABACER27. In contrast, LABACER27 induced higher levels of IL-10 in the respiratory tract than LABACER01. Genomic analysis revealed that K. pneumoniae LABACER01 and LABACER27 possess virulence factors found in other strains that have been shown to be hypervirulent, including genes required for enterobactin (entABCDEF) and salmochelin (iroDE) biosynthesis. In both strains, the genes of toxin-antitoxin systems, as well as regulators of the expression of virulence factors and adhesion genes were also detected. Studies on the genetic potential of multiresistant K. pneumoniae strains as well as their cellular and molecular interactions with the host are of fundamental importance to assess the association of certain virulence factors with the intensity of the inflammatory response. In this sense, this work explored the virulence profile based on genomic and in vivo studies of hypermucoviscous carbapenem-resistant K. pneumoniae ST25 strains, expanding the knowledge of the biology of the emerging ST25 clone in Argentina.


Asunto(s)
Enterobacteriaceae Resistentes a los Carbapenémicos , Infecciones por Klebsiella , Animales , Antibacterianos/farmacología , Argentina , Carbapenémicos/farmacología , Genómica , Infecciones por Klebsiella/tratamiento farmacológico , Infecciones por Klebsiella/epidemiología , Klebsiella pneumoniae , Ratones , Factores de Virulencia/genética , Factores de Virulencia/farmacología
6.
Arch Microbiol ; 203(7): 4351-4359, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34110479

RESUMEN

Multidrug-resistant (MDR) and hypervirulent Klebsiella pneumoniae (hvKp) clones have become a major threat to global public health. The clonal group 258 (CG258) is considered a high-risk CG and the K. pneumoniae strains belonging to it are often multi-resistant and to spread mainly in the hospital environment. This study aimed to characterize the antimicrobial resistance profile, virulence factors, and the clonal relationships among 13 K. pneumoniae strains belonging to CG258 from patients admitted to a tertiary hospital in Teresina, in the state of Piauí, northeastern Brazil. Ten strains were classified as MDR and three as extensively drug-resistant (XDR). Three different ß-lactamase-encoding genes (blaKPC, blaOXA-1-like, and blaCTX-M-Gp1) and six virulence genes (fimH, ycfM, mrkD, entB, ybtS, and kfu) were detected. Moreover, two hypermucoviscous K. pneumoniae strains and one capsular K-type 2 were found. Multilocus sequence typing analysis revealed ten different sequence types (STs) (ST14, ST17, ST20, ST29, ST45, ST101, ST268, ST1800, ST3995, and ST3996) belonging to CG258, being two (ST3995 and ST3996) described for the first time in this study.


Asunto(s)
Farmacorresistencia Bacteriana , Infecciones por Klebsiella , Klebsiella pneumoniae , Factores de Virulencia , Antibacterianos/farmacología , Brasil , Farmacorresistencia Bacteriana/genética , Humanos , Infecciones por Klebsiella/microbiología , Klebsiella pneumoniae/clasificación , Klebsiella pneumoniae/efectos de los fármacos , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/patogenicidad , Pruebas de Sensibilidad Microbiana , Tipificación de Secuencias Multilocus , Factores de Virulencia/genética
7.
J Infect Chemother ; 27(1): 55-61, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32888833

RESUMEN

INTRODUCTION: Extended spectrum beta-lactamase (ESBL)-producing Klebsiellapneumoniae is a serious concern for nosocomial infection and the emergence rate in Indonesia is higher than that in developed countries. The purpose of this study was to investigate the genetic characteristics of ESBL-producing K. pneumoniae isolated from UTI patients in Indonesia. MATERIALS AND METHODS: We collected K. pneumoniae resistant to ceftazidime or cefotaxime isolated from UTI patients in Dr. Soetomo's Academic Hospital in Surabaya, Indonesia in 2015. Ninety-four strains were identified as ESBL-producing bacteria by confirmation tests. The isolates were investigated by antimicrobial susceptibility testing with 20 drugs and ESBL gene detection, plasmid replicon typing and virulence genes as hypermucoviscous (HMV) strains were tested by the string test. RESULTS: High rates of resistance to ciprofloxacin (86.2%), tetracycline (80.9%) and nalidixic acid (78.7%) were observed. CTX-M-15 was the most common ESBL gene (89.4%), 33 of which also carried SHV-type ESBL. IncF was the most prevalent plasmid replicon typing (47.6%). Sixteen (17.0%) strains were judged as HMV, all of which had rmpA and more than half of which had fimH, uge, and wab. IncL/M was the most common replicon plasmid in the HMV strains, and the difference in the positive rate was statistically significant (p = 0.0024). CONCLUSION: This study showed the high prevalence of multiple-drug resistant and predominately CTX-M-15-positive ESBL-producing K. pneumoniae in Indonesia. There was a correlation between IncL/M and the HMV phenotype in this study. As such hypervirulent strains continue to emerge, studying their dissemination with resistance determinants is an urgent priority.


Asunto(s)
Infecciones por Klebsiella , Klebsiella pneumoniae , Antibacterianos/farmacología , Escherichia coli/genética , Humanos , Indonesia/epidemiología , Infecciones por Klebsiella/epidemiología , Klebsiella pneumoniae/genética , Pruebas de Sensibilidad Microbiana , Plásmidos/genética , beta-Lactamasas/genética
8.
J Intern Med ; 287(3): 283-300, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31677303

RESUMEN

Hypervirulent Klebsiella pneumoniae (hvKp) has emerged as a concerning global pathogen. hvKp is more virulent than classical K. pneumoniae (cKp) and capable of causing community-acquired infections, often in healthy individuals. hvKp is carried in the gastrointestinal tract, which contributes to its spread in the community and healthcare settings. First recognized in Asia, hvKp arose as a leading cause of pyogenic liver abscesses. In the decades since, hvKp has spread globally and causes a variety of infections. In addition to liver abscesses, hvKp is distinct from cKp in its ability to metastasize to distant sites, including most commonly the eye, lung and central nervous system (CNS). hvKp has also been implicated in primary extrahepatic infections including bacteremia, pneumonia and soft tissue infections. The genetic determinants of hypervirulence are often found on large virulence plasmids as well as chromosomal mobile genetic elements which can be used as biomarkers to distinguish hvKp from cKp clinical isolates. These distinct virulence determinants of hvKp include up to four siderophore systems for iron acquisition, increased capsule production, K1 and K2 capsule types, and the colibactin toxin. Additionally, hvKp strains demonstrate hypermucoviscosity, a phenotypic description of hvKp in laboratory conditions that has become a distinguishing feature of many hypervirulent isolates. Alarmingly, multidrug-resistant hypervirulent strains have emerged, creating a new challenge in combating this already dangerous pathogen.


Asunto(s)
Infecciones por Klebsiella/microbiología , Klebsiella pneumoniae/patogenicidad , Virulencia , Antibacterianos/farmacología , Infecciones Comunitarias Adquiridas/epidemiología , Farmacorresistencia Bacteriana , Humanos , Infecciones por Klebsiella/tratamiento farmacológico , Infecciones por Klebsiella/epidemiología , Klebsiella pneumoniae/efectos de los fármacos
9.
J Infect Chemother ; 26(1): 110-114, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31266705

RESUMEN

Unusual community-acquired invasive Klebsiella pneumoniae infection has been reported worldwide, particularly in Asia. Recently, several virulence-associated genes of the isolates have been investigated. We report a case of multifocal intramuscular and musculoskeletal abscesses caused by K. pneumoniae in a 61-year-old male diabetes patient. A string test of the K. pneumoniae isolate, which was recovered from abscesses obtained by surgical debridement and drainage, was positive. We used whole-genome sequencing to analyze the virulence-associated gene profile of the isolate. The isolate belonged to the K2 genotype with sequence type 375. The isolate harbored rmpA and rmpA2, which induce serum resistance (hypermucoviscosity). The isolate also carried siderophores, i.e., aerobactin and salmochelin, which are associated with enhanced bacterial growth. The isolate did not harbor K1-unique virulence factors, such as colibactin, microcin, and yersiniabactin. Our K2 strain harbored a combination of virulence plasmid-associated genes-rmpA/A2 and siderophores (aerobactin and salmochelin). Hence, we advocate that essential molecular virulence factors of isolates that cannot be identified by a string test and capsular serotyping alone may exist.


Asunto(s)
Complicaciones de la Diabetes , Infecciones por Klebsiella , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/patogenicidad , Infecciones de los Tejidos Blandos , Factores de Virulencia/genética , ADN Bacteriano/genética , Complicaciones de la Diabetes/diagnóstico , Complicaciones de la Diabetes/microbiología , Mano/microbiología , Mano/patología , Humanos , Infecciones por Klebsiella/complicaciones , Infecciones por Klebsiella/diagnóstico , Infecciones por Klebsiella/microbiología , Masculino , Persona de Mediana Edad , Tipificación Molecular , Infecciones de los Tejidos Blandos/complicaciones , Infecciones de los Tejidos Blandos/diagnóstico , Infecciones de los Tejidos Blandos/microbiología , Secuenciación Completa del Genoma
10.
Acta Microbiol Immunol Hung ; 67(2): 120-126, 2020 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-32619189

RESUMEN

Hypervirulent Klebsiella pneumoniae (hvKP) strains are associated with vigorous clinical presentation and relapses. Initially reported from Asia, these variants have spread globally and become an emerging agent of significant health threat. This study was carried out to identify hvKP strains in a previously uninvestigated region and to evaluate the impact of commonly-employed phenotypic and genotypic markers as diagnostic assays. A total of 111 blood culture isolates, collected at a tertiary care center was investigated. The hvKP strains were sought by a string test and the amplification of partial magA, rmpA, iucA and peg344. All products were characterized via sequencing. Evidence for hvKP was observed in 10.8% via iucA amplification (7.2%), string test (2.7%) and magA amplification (0.9%). Specific products were not produced by assays targeting rmpA and peg344 genes. Antibiotic susceptibility patterns compatible with possible extensive or pan-antimicrobial resistance was noted in 66.7% of the hvKP candidate strains. Capsule type in the magA positive strain was characterized as K5. We have detected hvKP in low prevalence at a region with no prior documentation. Targetting the aerobactin gene via iucA amplification provided the most accurate detection in this setting. The epidemiology of hvKP in Anatolia requires elucidation for effective control and management.


Asunto(s)
Antibacterianos/uso terapéutico , Farmacorresistencia Bacteriana Múltiple/genética , Infecciones por Klebsiella/diagnóstico , Infecciones por Klebsiella/tratamiento farmacológico , Klebsiella pneumoniae/genética , Adolescente , Adulto , Anciano , Proteínas Bacterianas/genética , Niño , Preescolar , Femenino , Humanos , Lactante , Infecciones por Klebsiella/epidemiología , Klebsiella pneumoniae/aislamiento & purificación , Klebsiella pneumoniae/patogenicidad , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Centros de Atención Terciaria , Turquía/epidemiología , Virulencia/genética , Factores de Virulencia/genética , Adulto Joven
11.
Artículo en Inglés | MEDLINE | ID: mdl-30803966

RESUMEN

The convergence of hypervirulence and multidrug resistance in Klebsiella pneumoniae is a significant concern. Here, we report the first screen for hypermucoviscosity, a trait associated with increased virulence, using a U.S. surveillance collection of carbapenem-resistant (CR) K. pneumoniae isolates. We identified one hypermucoviscous isolate, which carried a gene encoding the KPC-3 carbapenemase, among numerous resistance genes. The strain further exhibited colistin heteroresistance undetected by diagnostics. This convergence of diverse resistance mechanisms and increased virulence underscores the need for enhanced K. pneumoniae surveillance.


Asunto(s)
Enterobacteriaceae Resistentes a los Carbapenémicos/genética , Carbapenémicos/farmacología , Colistina/farmacología , Enterobacteriaceae Resistentes a los Carbapenémicos/efectos de los fármacos , Farmacorresistencia Bacteriana/genética , Genotipo , Klebsiella pneumoniae/efectos de los fármacos , Klebsiella pneumoniae/genética , Pruebas de Sensibilidad Microbiana , Virulencia
12.
Ann Clin Microbiol Antimicrob ; 18(1): 4, 2019 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-30665418

RESUMEN

BACKGROUND: The definition of hypervirulent Klebsiella pneumoniae (hvKp), traditionally regarded as hypermucoviscosity, is controversial. However, data based on both phenotype (hypermucoviscous) and genetic (aerobactin) criteria are limited. METHODS: A retrospective study was conducted in 175 geriatric patients between January 2008 and January 2014. The clinical and molecular data, including antimicrobial susceptibility testing, extended-spectrum-ß-lactamase (ESBL) production, virulence gene, and multilocus sequence typing of the hvKp-group (hypermucoviscosity and aerobactin positive) were compared with those of classic K. pneumoniae (cKp) isolates. RESULTS: Of 175 Kp isolates, 45.7% were hvKp. In pathogenicity, K1, K2, magA, rmpA, and rmpA2 genes were strongly associated with hvKp (P < 0.01). In the hvKp group, invasive infections (P < 0.000), liver abscess (P = 0.008), abdominal infection (P = 0.002) and septic shock (P = 0.035) are significantly higher than cKp group. Patients with better nutritional status were frequently infected with hvKp. However, host inflammatory reaction is most severe in hvKp group. Patients with diabetes (odds ratio [OR] = 2.548) and digestive diseases (OR = 2.196) are more likely to be infected with hvKp. Importantly, the detection of hvKp isolates increased from January 2008 to January 2010, January 2010 to January 2012, and January 2010 to January 2014 (12, 30, and 48 isolates, respectively). Overall, 16.3% of hvKp isolates produced ESBLs and 20.0% were MDR-hvKp. Multivariate analysis implied that infection occurred in the ICU (OR = 5.826) and patients with indwelling stomach tubes (OR = 6.461) are independent risk factors for ESBL-hvKp infection. CONCLUSIONS: HvKp, especially ESBL-hvKp and MDR-hvKp, is emerging in the elderly. It is essential to enhance clinical awareness and management of hvKp infections.


Asunto(s)
Farmacorresistencia Bacteriana/genética , Ácidos Hidroxámicos , Infecciones por Klebsiella/epidemiología , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/patogenicidad , Epidemiología Molecular , Factores de Virulencia/genética , Anciano , Anciano de 80 o más Años , Antibacterianos , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , China/epidemiología , Complicaciones de la Diabetes , Humanos , Infecciones por Klebsiella/microbiología , Klebsiella pneumoniae/aislamiento & purificación , Tipificación de Secuencias Multilocus , Estudios Retrospectivos , Factores de Riesgo , Virulencia/genética , beta-Lactamasas/genética
15.
Microb Pathog ; 124: 301-304, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30165112

RESUMEN

Hypervirulent variants of klebsiella pneumoniae (hvKP), which cause serious infections not only healthy individuals, but also the immunocompromised patients, have been increasingly reported recently. One conjugation of a hypermucoviscous strian SWU01 co-carried the resistance gene blaKPC-2 and virulence gene iroN by the PCR detection from three carbapenem-resistance hvKP. To know the genetic context of this plasmid. The whole genome of this strain was sequenced. We got a 162,552-bp plasmid (pSWU01) which co-carried the resistance gene blaKPC-2 and virulence gene iroN. It is composed of a typical IncFII-type backbone, five resistance genes including blaCTX-M-65, blaKPC-2, blaSHV-12, blaTEM-1 and rmtB, and several virulence relevant factors including iroN, traT and toxin-antitoxin systems. The plasmid pSWU01 co-carrying the multidrug resistance determinants and virulence relevant factors from the hypermucoviscous K. pneumoniae represents a novel therapeutic challenge.


Asunto(s)
Proteínas Bacterianas/metabolismo , Infecciones por Klebsiella/microbiología , Klebsiella pneumoniae/enzimología , Factores de Virulencia/metabolismo , beta-Lactamasas/metabolismo , Antibacterianos/farmacología , Proteínas Bacterianas/genética , Humanos , Klebsiella pneumoniae/efectos de los fármacos , Klebsiella pneumoniae/genética , Metiltransferasas/genética , Metiltransferasas/metabolismo , Plásmidos/genética , Plásmidos/metabolismo , Transporte de Proteínas , Factores de Virulencia/genética , beta-Lactamasas/genética
16.
BMC Infect Dis ; 18(1): 358, 2018 07 31.
Artículo en Inglés | MEDLINE | ID: mdl-30064360

RESUMEN

BACKGROUND: Klebsiella pneumoniae bloodstream infections (BSIs) occur with significant prevalence and high mortality worldwide. Antimicrobial resistance and virulence are two main factors participating in the pathogenicity of K. pneumoniae. Here we investigated the prevalence of blaKPC and virulence factors in K. pneumoniae isolated from patients with BSIs and their association with clinical outcome. METHODS: The clinical data of 285 K. pneumoniae BSI cases diagnosed from January 2013 to December 2015 in a Chinese university hospital were retrospectively evaluated. The "string test" was performed to identify hypermucoviscous K. pneumoniae (HMKP). blaKPC, rmpA, magA and serotype-specific genes were detected by PCR amplification. Finally, a Cox proportional hazards model was employed to determine the predictors of 14-day mortality. RESULTS: Of these isolates, the prevalence of blaKPC and rmpA were 33.3% (95/285) and 31.6% (90/285) respectively. 69 isolates (24.2%, 69/285) were HMKP. rmpA was strongly associated with HM phenotype. The KPC-producing KP and HMKP were almost non-overlapping and only three HMKP isolates harbored blaKPC. K1 (28, 40.6%) and K2 (22, 31.9%) were the most common serotypes in HMKP. 44.9% of HMKP BSIs had origin of biliary tract infection or liver abscess. The 14-day mortality was 100% in blaKPC+/HM+ subgroup (3/3), followed by blaKPC+/HM- (39/92, 42.4%), blaKPC-/HM+ (5/66, 7.6%) and blaKPC-/HM- (7/124, 5.6%). The 14-day cumulative survival was significantly different between blaKPC+ and blaKPC- subgroup (Log-rank p < 0.001) but almost equal between blaKPC-/HM+ and blaKPC-/HM- subgroup (Log-rank p = 0.578) under the condition of comparable illness severity between blaKPC-/HM+ and blaKPC-/HM- subgroup. Independent risk factors for 14-day mortality were Pitt bacteremia score (HR 1.24, CI 95% 1.13-1.36, p < 0.001), Charlson comorbidity index (HR 1.24, CI 95% 1.09-1.41, p = 0.001), septic shock (HR 2.61, CI 95% 1.28-5.35, p = 0.009) and blaKPC (HR 2.20, CI 95% 1.06-4.54, p = 0.034). CONCLUSIONS: Most of HMKP were antibiotic-susceptible and people infected received appropriate antimicrobial therapy, which may explain the favorable outcome of HMKP BSIs. The KPC-producing HMKP BSIs were scarce but life-threatening. blaKPC was valuable in predicting 14-day mortality.


Asunto(s)
Bacteriemia/diagnóstico , Bacteriemia/epidemiología , Infecciones por Klebsiella/diagnóstico , Infecciones por Klebsiella/epidemiología , Klebsiella pneumoniae , beta-Lactamasas/genética , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Bacteriemia/microbiología , Femenino , Hospitales Universitarios , Humanos , Infecciones por Klebsiella/sangre , Infecciones por Klebsiella/tratamiento farmacológico , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/aislamiento & purificación , Masculino , Persona de Mediana Edad , Prevalencia , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Serogrupo , Análisis de Supervivencia , Resultado del Tratamiento , Virulencia/genética , Factores de Virulencia/genética
17.
Vet Pathol ; 54(5): 846-850, 2017 09.
Artículo en Inglés | MEDLINE | ID: mdl-28494709

RESUMEN

Tissues of stranded California sea lions ( Zalophus californianus) naturally infected with a hyperviruluent strain of Klebsiella pneumoniae were examined by histopathology and immunohistochemistry against the K. pneumoniae K2 capsular antigen. In 7 of 8 animals, there was severe purulent bronchopneumonia, sometimes complicated by fibrinonecrotizing pleuritis with pyothorax. In affected areas of lung, large numbers of degenerate neutrophils and macrophages were admixed with rare large extracellular and intracellular gram-negative bacilli surrounded by a prominent capsule. Through serotyping, polymerase chain reaction, sequencing, and immunohistochemistry, these bacteria were confirmed to be a K2 serotype of K. pneumoniae. The same bacteria were identified through double immunolabeling within macrophages in blood vessels, lymph nodes, spleen, and liver. Intact K. pneumoniae were identified on epithelial surfaces of the nasopharyngeal, tracheal, and small intestine mucosae and within distal renal tubules. Our findings indicate that hypervirulent K. pneumoniae causes severe respiratory disease and intrahistiocytic bacteremia in California sea lions.


Asunto(s)
Infecciones por Klebsiella/veterinaria , Klebsiella pneumoniae/patogenicidad , Neumonía/veterinaria , Leones Marinos/microbiología , Animales , Antígenos Bacterianos/inmunología , Cápsulas Bacterianas/inmunología , California , Femenino , Inmunohistoquímica/veterinaria , Infecciones por Klebsiella/diagnóstico , Infecciones por Klebsiella/microbiología , Infecciones por Klebsiella/patología , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/inmunología , Masculino , Neumonía/diagnóstico , Neumonía/microbiología , Neumonía/patología , Reacción en Cadena de la Polimerasa/veterinaria , Serogrupo , Virulencia
18.
J Infect Dis ; 214(12): 1865-1875, 2016 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-27683817

RESUMEN

Klebsiella pneumoniae remains an important cause of intrapulmonary infection and invasive disease worldwide. K. pneumoniae can evade serum killing and phagocytosis primarily through the expression of a polysaccharide capsule, but its pathogenicity is also influenced by host factors. We examined whether CD36, a scavenger receptor that recognizes pathogen and modified self ligands, is a host determinant of K. pneumoniae pathogenicity. Despite differences in serum sensitivity and virulence of 3 distinct K. pneumoniae (hypermucoviscous K1, research K2, and carbapenemase-producing ST258) strains, the absence of CD36 significantly increased host susceptibility to acute intrapulmonary infection by K. pneumoniae, regardless of strain. We demonstrate that CD36 enhances LPS responsiveness to K. pneumoniae to increase downstream cytokine production and macrophage phagocytosis that is independent of polysaccharide capsular antigen. Our study provides new insights into host determinants of K. pneumoniae pathogenicity and raises the possibility that functional mutations in CD36 may predispose individuals to K. pneumoniae syndromes.


Asunto(s)
Antígenos CD36/metabolismo , Interacciones Huésped-Patógeno , Infecciones por Klebsiella/inmunología , Klebsiella pneumoniae/inmunología , Lipopolisacáridos/inmunología , Macrófagos/inmunología , Fagocitosis , Animales , Femenino , Macrófagos/microbiología , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Neumonía Bacteriana/inmunología
19.
BMC Infect Dis ; 16(1): 680, 2016 11 16.
Artículo en Inglés | MEDLINE | ID: mdl-27852233

RESUMEN

BACKGROUND: A few Japanese cases of hypermucoviscous Klebsiella pneumoniae (K. pneumoniae) invasive syndrome have recently been reported. Although extrahepatic complications from bacteremic dissemination have been observed, infected aneurysms are rare. Furthermore, the primary source of infection is generally a liver abscess, and is rarely the prostate. Therefore, we report two atypical cases of hypermucoviscous K. pneumoniae invasive syndrome. CASE PRESENTATION: The first case was an 81-year-old Japanese man with no significant medical history, who was referred to our hospital for vision loss in his right eye. Contrast-enhanced whole-body computed tomography revealed abscesses in the liver and the prostate, and an infected left internal iliac artery aneurysm. Contrast-enhanced head magnetic resonance imaging revealed brain abscesses. Cultures of the liver abscess specimen and aqueous humor revealed K. pneumoniae with the hypermucoviscosity phenotype, which carried the magA gene (mucoviscosity-associated gene A) and the rmpA gene (regulator of mucoid phenotype A). We performed enucleation of the right eyeball, percutaneous transhepatic drainage, coil embolization of the aneurysm, and administered a 6-week course of antibiotic treatment. The second case was a 69-year-old Japanese man with diabetes mellitus, who was referred to our hospital with fever, pollakiuria, and pain on urination. Contrast-enhanced whole-body computed tomography revealed lung and prostate abscesses, but no liver abscesses. Contrast-enhanced head magnetic resonance imaging revealed brain abscesses. The sputum, urine, prostate abscess specimen, and aqueous humor cultures revealed K. pneumoniae with the hypermucoviscosity phenotype, which carried magA and rmpA. We performed enucleation of the left eyeball, percutaneous drainage of the prostate abscess, and administered a 5-week course of antibiotic treatment. CONCLUSIONS: Hypermucoviscous K. pneumoniae can cause infected aneurysms, and the prostate can be the primary site of infection. We suggest that a diagnosis of hvKP invasive syndrome should be considered in all patients who present with K. pneumoniae infection and multiple organ abscesses.


Asunto(s)
Infecciones por Klebsiella/etiología , Infecciones por Klebsiella/terapia , Anciano , Anciano de 80 o más Años , Bacteriemia/etiología , Bacteriemia/terapia , Proteínas Bacterianas/genética , Diabetes Mellitus , Humanos , Infecciones por Klebsiella/diagnóstico , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/patogenicidad , Absceso Hepático/microbiología , Imagen por Resonancia Magnética , Masculino , Enfermedades de la Próstata/microbiología , Enfermedades de la Próstata/terapia , Síndrome , Tomografía Computarizada por Rayos X
20.
Infect Drug Resist ; 17: 2685-2699, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38953096

RESUMEN

Background: The occurrence and dissemination of hypermucoviscous and hypervirulent Klebsiella pneumoniae (hm-hvKp) isolates in clinical settings are a critical public health problem in the world. However, the data on these isolates in community populations are limited. This study aims to understand the prevalence and molecular characteristics of hm-hvKp isolates in community patients in Shanghai, China. Methods: In 2018, an active surveillance system focused on hm-hvKp in community diarrhoeal cases was implemented in Pudong New Area, Shanghai, China, involving 12 sentinel hospitals. The antimicrobial susceptibility of hm-hvKp isolates from fecal samples was tested, and whole-genome sequencing (WGS) was performed to predict the serotypes and sequence types and to identify antimicrobial resistance determinants, virulence determinants, and phylogenetic clusters. Results: The overall prevalence of hm K. pneumoniae isolates was 2.48% (31/1252), with the proportions of 1.76% (22/1252) for hm-hvKp and 0.72% (9/1252) for hm not hv K. pneumoniae. The prevalence of hm-hvKp isolates among different age groups and different months was statistically significant. All the 22 hm-hvKp isolates were susceptible to 20 antimicrobial agents and only carried bla SHV gene, and KL1 and KL2 accounted for eight (36.36%) cases and seven (31.82%) cases, respectively. The eight ST23/KL1 isolates belonged to the predominant CG23-I clade, which typically possessed the virulence determinants profile of rmpA/rmpA2-iro-iuc-ybt-irp-clb. The five ST86/KL2 isolates were assigned to the global clusters ST86/KL2-1 (n=2), ST86/KL2-2 (n=2), ST86/KL2-3 (n=1), all lack of the clb gene. Shanghai ST23/KL1 and ST86/KL2 isolates were closely related to the global isolates from liver abscesses, blood, and urine. Conclusion: Hm-hvKp is carried by the community population of Shanghai, with ST23/KL1 and ST86/KL2 isolates predominant. Hm-hvKp isolates of different continents, different sources, and different virulence levels were closely related. Ongoing surveillance of hm-hvKp isolates in the community population is warranted.

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