The intrinsic resistome of Klebsiella pneumoniae

Bernardini, Alejandra; Cuesta, Trinidad; Axelsson, Tomas; Bengoechea, José A.; Martínez, José Luis; Sánchez, María Blanca

doi:10.1016/j.ijantimicag.2018.09.012

Cited by 24 publications

(12 citation statements)

References 38 publications

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“…The resistance to some β-lactams in K. pneumoniae species is intrinsic because some of the resistance genes exist in the chromosome. For instance, the SHV gene is regularly existed in the chromosome and conferring resistance against ampicillin [46,47]. Other β-lactamases could be a part of the accessory genome [48].…”

Section: Discussionmentioning

confidence: 99%

Incidence and Antibiotic Sensitivity of Klebsiella pneumonia isolated from urinary tract infection patients in Zakho emergency hospital / Iraq

Polse¹,

Qarani²,

Assafi³

et al. 2020

J.Edu.Sci.

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Uropathogenic Klebsiella pneumoniae is considered the most important causes of urinary tract infection, and recently the antibiotic resistance of this pathogen has increased dramatically. The study aims at investigating the prevalence and antibiotic sensitivity of uropathogenic K. pneumoniae among different ages of groups at both genders. 1737 urine specimens were collected from individuals admitted to Zakho emergency hospital from January 2016 until December 2018. K. pneumoniae was identified based on Gram stain, colony characteristics and biochemical tests, and then it was tested for their antibiotic sensitivity. Out of all samples, 1076 (61.9%) showed significant bacterial yield. The UTIs among females (64.3%) were statistically higher than males (46.5%) (P < 0.001). The age group of 20-29 years was highly susceptible to UTIs (43%). Among the total UTIs, K. pneumoniae represented 16.2%. K. pneumoniae in males (23.4%) was significantly higher than females (15.4%) (P=0.03). The age group 40-49 years (32.2%) was the highest group that at risk for K. pneumoniae infection. K. pneumoniae was highly susceptible to imipenem (100%) and was highly resistant against cephalothin (90.8%). A high prevalence of UTIs were observed among the age group of 20-29 years and the females had more risk of having UTIs. The males were more susceptible to K. pneumoniae with higher prevalence in the age group of 40-49 years. K. pneumoniae showed high sensitivity toward imipenem and high resistance to cephalothin. More awareness is required in all healthcare sectors for regular surveillance of the use of antimicrobial agents to reduce the resistance rates and to eradicate the pathogens.

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Section: Discussionmentioning

confidence: 99%

Incidence and Antibiotic Sensitivity of Klebsiella pneumonia isolated from urinary tract infection patients in Zakho emergency hospital / Iraq

Polse¹,

Qarani²,

Assafi³

et al. 2020

J.Edu.Sci.

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“…Concerning the target, elements that reduce its affinity with the antibiotic include mutations ( 5 ), target protection ( 6 ), bypass ( 7 ) or replacement ( 8 ) and eventually increased target expression ( 9 ). Studies of the intrinsic resistome have shown that, in addition to these classical resistance determinants, the susceptibility to antibiotics of a bacterial species depends on the activity of several elements encompassing all functional categories ( 10 – 12 ). However, little is still known about the interplay between bacterial metabolism and the acquisition of AR ( 13 ).…”

Section: Introductionmentioning

confidence: 99%

The Inactivation of Enzymes Belonging to the Central Carbon Metabolism Is a Novel Mechanism of Developing Antibiotic Resistance

et al. 2020

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Fosfomycin is a bactericidal antibiotic, analogous to phosphoenolpyruvate, that exerts its activity by inhibiting the activity of MurA. This enzyme catalyzes the first step of peptidoglycan biosynthesis, the transfer of enolpyruvate from phosphoenolpyruvate to uridine-diphosphate-N-acetylglucosamine. Fosfomycin is increasingly being used, mainly for treating infections caused by Gram-negative multidrug-resistant bacteria. The mechanisms of mutational resistance to fosfomycin in Stenotrophomonas maltophilia, an opportunistic pathogen characterized by its low susceptibility to commonly used antibiotics, were studied in the current work. None of the mechanisms reported so far for other organisms, which include the production of fosfomycin-inactivating enzymes, target modification, induction of an alternative peptidoglycan biosynthesis pathway, and the impaired entry of the antibiotic, are involved in the acquisition of such resistance by this bacterial species. Instead, the unique cause of resistance in the mutants studied is the mutational inactivation of different enzymes belonging to the Embden-Meyerhof-Parnas central metabolism pathway. The amount of intracellular fosfomycin accumulation did not change in any of these mutants, showing that neither inactivation nor transport of the antibiotic is involved. Transcriptomic analysis also showed that the mutants did not present changes in the expression level of putative alternative peptidoglycan biosynthesis pathway genes or any related enzyme. Finally, the mutants did not present an increased phosphoenolpyruvate concentration that might compete with fosfomycin for its binding to MurA. On the basis of these results, we describe a completely novel mechanism of antibiotic resistance based on mutations of genes encoding metabolic enzymes. IMPORTANCE Antibiotic resistance has been largely considered a specific bacterial response to an antibiotic challenge. Indeed, its study has been mainly concentrated on mechanisms that affect the antibiotics (mutations in transporters, efflux pumps, and antibiotic-modifying enzymes, or their regulators) or their targets (i.e., target mutations, protection, or bypass). Usually, antibiotic resistance-associated metabolic changes were considered a consequence (fitness costs) and not a cause of antibiotic resistance. Herein, we show that alterations in the central carbon bacterial metabolism can also be the cause of antibiotic resistance. In the study presented here, Stenotrophomonas maltophilia acquires fosfomycin resistance through the inactivation of glycolytic enzymes belonging to the Embden-Meyerhof-Parnas pathway. Besides resistance to fosfomycin, this inactivation also impairs the bacterial gluconeogenic pathway. Together with previous work showing that antibiotic resistance can be under metabolic control, our results provide evidence that antibiotic resistance is intertwined with the bacterial metabolism.

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“…Massively parallel sequencing combined with traditional transposon mutagenesis [101] , as well as high-throughput screening of transposon insertion libraries, have been used to track genes whose inactivation modifies the susceptibility to antibiotics [102] , [103] . This method has been used to analyse the resistome of different pathogens, including Pseudomonas aeruginosa [104] , [105] , [106] , [107] , [108] , [109] , [110] , [111] , [112] , [113] , [114] , [115] , [116] , [117] , [118] , [119] , E. coli [110] , Staphylococcus aureus [111] , [112] or Klebsiella pneumoniae [113] , among other bacteria [114] , [115] .…”

Section: Genomic Approaches For the Study Of Antibiotic Resistancementioning

confidence: 99%

Antibiotic resistance: Time of synthesis in a post-genomic age

Gil-Gil

Ochoa-Sánchez

Baquero

et al. 2021

Computational and Structural Biotechnology Journal

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The intrinsic resistome of Klebsiella pneumoniae

Cited by 24 publications

References 38 publications

Incidence and Antibiotic Sensitivity of Klebsiella pneumonia isolated from urinary tract infection patients in Zakho emergency hospital / Iraq

Incidence and Antibiotic Sensitivity of Klebsiella pneumonia isolated from urinary tract infection patients in Zakho emergency hospital / Iraq

The Inactivation of Enzymes Belonging to the Central Carbon Metabolism Is a Novel Mechanism of Developing Antibiotic Resistance

Antibiotic resistance: Time of synthesis in a post-genomic age

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