Hypermucoviscous Klebsiella pneumoniae: A challenge in community acquired infection

Sánchez-López, Javier; García-Caballero, Andrea; Francisco, Carolina Navarro-San; Quereda, Carmen; Ruíz-Garbajosa, Patricia; Navas, Enrique; Dronda, Fernando; Morosini, María Isabel; Cantón, Rafael; Díez-Aguilar, María

doi:10.1016/j.idcr.2019.e00547

Cited by 45 publications

(42 citation statements)

References 15 publications

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“…The Gram-negative bacillus K. pneumoniae is a leading cause of healthcare-associated infections, including urinary tract infections, surgical sites infections, soft tissues infections, bacteremia and pneumonia [11]. In the 1980s, case reports from Taiwan described community acquired liver abscesses caused by hvKp in patients with serious concomitant endorgan manifestations, such as meningitis and endophthalmitis [12]. Since the first report in Taiwan, hvKPs have been observed with increasing frequency in many countries in Asia, Europe and America [12].…”

Section: Discussionmentioning

confidence: 99%

“…In the 1980s, case reports from Taiwan described community acquired liver abscesses caused by hvKp in patients with serious concomitant endorgan manifestations, such as meningitis and endophthalmitis [12]. Since the first report in Taiwan, hvKPs have been observed with increasing frequency in many countries in Asia, Europe and America [12]. It is well known that hvKp can invade many organs in patient, including liver.…”

Section: Discussionmentioning

confidence: 99%

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Effects of iron on the growth, biofilm formation and virulence of Klebsiella pneumoniae causing liver abscess

et al. 2020

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Background: Klebsiella pneumoniae is considered the most clinically relevant species of Enterobacteriaceae, known to cause severe infections including liver abscesses. To the best of our knowledge, a large proportion of iron in the human body is accumulated and stored in the liver. We hypothesize that increased iron availability is an important factor driving liver abscess formation and we therefore aim to understand the effects of iron on K. pneumoniae causing liver abscesses. Results: All tested K. pneumoniae clinical isolates, including those isolated from liver abscesses and other abdominal invasive infection sites, grew optimally when cultured in LB broth supplemented with 50 μM iron and exhibited the strongest biofilm formation ability under those conditions. Decreased growth and biofilm formation ability were observed in all tested strains when cultured with an iron chelator (P < 0.05). The infection model of G. mellonella larvae indicated the virulence of liver abscess-causing K. pneumoniae (2/3) cultured in LB broth with additional iron was significantly higher than those under iron-restricted conditions (P < 0.05). The relative expression levels of the four siderophore genes (iucB, iroB, irp1, entB) in K. pneumoniae strains isolated from liver abscesses cultured with additional iron were lower than those under iron-restricted conditions (P < 0.05).Conclusions: It is suggested by our research that iron in the environment can promote growth, biofilm formation and enhance virulence of K. pneumoniae causing liver abscesses. A lower expression of siderophore genes correlates with increased virulence of liver abscess-causing K. pneumoniae. Further deeper evaluation of these phenomena is warranted.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Effects of iron on the growth, biofilm formation and virulence of Klebsiella pneumoniae causing liver abscess

et al. 2020

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“…Klebsiella pneumoniae , a Gram-negative bacteria, causes ample number of life-threating diseases, including pneumonia, urinary tract infection, cystitis, endocarditis, sepsis, and blood stream infections and are the leading source of hospital acquired (nosocomial) infections ( Paczosa and Mecsas, 2016 ). They are also the leading cause of the worst community-acquired infections like pyogenic liver abscesses, endogenous endophthalmitis, and necrotizing pneumoniae ( Sánchez-López et al, 2019 ). The main reservoirs of K. pneumoniae are the gastrointestinal tract and medical personnel and equipment ( Podschun and Ullmann, 1998 ).…”

Section: Introductionmentioning

confidence: 99%

Conserved G-Quadruplex Motifs in Gene Promoter Region Reveals a Novel Therapeutic Approach to Target Multi-Drug Resistance Klebsiella pneumoniae

et al. 2020

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An opportunistic pathogen, Klebsiella pneumoniae is known to cause life-threating nosocomial infection with a high rate of morbidity and mortality. Evolutions of multi-drug-resistant and hyper-virulent strains of K. pneumoniae make the situation worse. Currently, there is no incisive drug molecule available for drug-resistant hyper-virulent K. pneumoniae infection that emphasizes the need for identification of novel and more promising drug targets in K. pneumoniae . Recently, various non-canonical structures of nucleic acids especially G-quadruplex (G4) motifs have been identified as potential therapeutic targets against several human pathogenic bacteria and viruses including Mycobacterium tuberculosis , Streptococcus pneumoniae , human immunodeficiency virus (HIV), Ebola, and Nipah. Therefore, in present study we screened the K. pneumoniae genomes for identification of evolutionary conserved G4 structure-forming motifs as promising anti-bacterial drug targets. Bioinformatics analysis revealed the presence of six highly conserved G4 motifs in the promoter region of five essential genes that play a critical role in nutrient transport and metabolism. Biophysical studies showed the formation of G4 structure by these conserved motifs. Circular Dichroism melting analysis showed the stabilization of these G4 motifs by a well-known G4-stabilizing agent, BRACO-19. The stabilization of these motifs by BRACO-19 was also able to stop the primer extension process, which is an essential phenomenon for expression of the G4-harboring gene. The addition of G4-specific ligand at low micromolar range was observed to be lethal for the growth of this bacteria and negatively controlled the expression of the G4-harboring genes via G4 structure stabilization. These observations strengthen the formation of G4 structures by the predicted G4 motif in vivo , which can be stabilized by G4 ligands like BRACO-19. This stabilization of G4 structures can attenuate the expression of G4-harboring essential genes and thus play a critical role in the regulation of gene expression. Thus, taking all given result in consideration, for the first time, this study showed the new therapeutic avenue for combating K. pneumoniae infection by characterizing the conserved G4 motifs as promising therapeutic targets.

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“…The Gram-negative bacillus K. pneumoniae is a leading cause of healthcare-associated infections, including urinary tract infections, surgical sites infections, soft tissues infections, bacteremia and pneumonia [18]. In the 1980s, case reports from Taiwan described community acquired liver abscesses caused by hvKp in patients with serious concomitant endorgan manifestations, such as meningitis and endophthalmitis [19]. Since the first report in Taiwan, hvKPs have been observed with increasing frequency in many countries in Asia, Europe and America [19].…”

Section: Discussionmentioning

confidence: 99%

“…In the 1980s, case reports from Taiwan described community acquired liver abscesses caused by hvKp in patients with serious concomitant endorgan manifestations, such as meningitis and endophthalmitis [19]. Since the first report in Taiwan, hvKPs have been observed with increasing frequency in many countries in Asia, Europe and America [19]. It is well known that hvKp can invade many organs in patient, including liver.…”

Section: Discussionmentioning

confidence: 99%

Effects of iron on the growth, biofilm formation and virulence of Klebsiella pneumoniae causing liver abscess

Chen

Dong

Zhang

et al. 2020

Preprint

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Background: Klebsiella pneumoniae is considered the most clinically relevant species of Enterobacteriaceae, known to cause severe infections including liver abscesses. To the best of our knowledge, a large proportion of iron in the human body is accumulated and stored in the liver. We hypothesize that increased iron availability is an important factor driving liver abscess formation and we therefore aim to understand the effects of iron on K. pneumoniae causing liver abscesses. Results: All tested K. pneumoniae clinical isolates, including those isolated from liver abscesses and other abdominal invasive infection sites, grew optimally when cultured in LB broth supplemented with 50 μM iron and exhibited the strongest biofilm formation ability under those conditions. Decreased growth and biofilm formation ability were observed in all tested strains when cultured with an iron chelator (P<0.05). The infection model of G. mellonella larvae indicated the virulence of liver abscess-causing K. pneumoniae (2/3) cultured in LB broth with additional iron was significantly higher than those under iron-restricted conditions (P<0.05). The relative expression levels of the four siderophore genes (iucB, iroB, irp1, entB) in K. pneumoniae strains isolated from liver abscesses cultured with additional iron were lower than those under iron-restricted conditions (P<0.05). Conclusions: It is suggested by our research that iron in the environment can promote growth, biofilm formation and enhance virulence of K. pneumoniae causing liver abscesses. A lower expression of siderophore genes correlates with increased virulence of liver abscess-causing K. pneumoniae. Further deeper evaluation of these phenomena is warranted.

show abstract

Hypermucoviscous Klebsiella pneumoniae: A challenge in community acquired infection

Cited by 45 publications

References 15 publications

Effects of iron on the growth, biofilm formation and virulence of Klebsiella pneumoniae causing liver abscess

Effects of iron on the growth, biofilm formation and virulence of Klebsiella pneumoniae causing liver abscess

Conserved G-Quadruplex Motifs in Gene Promoter Region Reveals a Novel Therapeutic Approach to Target Multi-Drug Resistance Klebsiella pneumoniae

Effects of iron on the growth, biofilm formation and virulence of Klebsiella pneumoniae causing liver abscess

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