Structural modification of LPS in colistin-resistant, KPC-producing Klebsiella pneumoniae

Leung, Lisa M.; Cooper, Vaughn S.; Rasko, David A.; Guo, Qinglan; Pacey, Marissa P; McElheny, Christi L.; Mettus, Roberta T.; Yoon, Sung Hwan; Goodlett, David R.; Ernst, Robert K.; Doi, Yohei

doi:10.1093/jac/dkx234

Cited by 70 publications

(66 citation statements)

References 28 publications

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“…102 Interestingly, in both K. pneumoniae and A. baumannii, genomic sequencing studies have found mutations in a common regulatory pathway controlling LPS modification systems, indicating that LPS modification is key to resistance in both species. [103][104][105] This genomederived hypothesis that altered LPS modification underlies resistance was ultimately confirmed for both organisms by comparing LPS modifications in susceptible and resistant isolates. 103,106 An important caveat in studying resistance evolution in individual patients is that the larger epidemiological significance of observed resistance mutations or mechanisms cannot necessarily be inferred.…”

Section: Mutational Modes Of Resistancementioning

confidence: 90%

“…[103][104][105] This genomederived hypothesis that altered LPS modification underlies resistance was ultimately confirmed for both organisms by comparing LPS modifications in susceptible and resistant isolates. 103,106 An important caveat in studying resistance evolution in individual patients is that the larger epidemiological significance of observed resistance mutations or mechanisms cannot necessarily be inferred. This disconnect between short-term and long-term impacts of resistance evolution is due to fitness costs associated with resistance that might limit the ultimate viability of resistant mutants once the selective pressure of the drug is removed.…”

Section: Mutational Modes Of Resistancementioning

confidence: 90%

“…The prospect of widespread colistin resistance is of great concern, as there are limited treatment options beyond colistin for the treatment of infections caused by carbapenemase‐producing Gram‐negatives, such as K. pneumoniae and A. baumannii . Interestingly, in both K. pneumoniae and A. baumannii , genomic sequencing studies have found mutations in a common regulatory pathway controlling LPS modification systems, indicating that LPS modification is key to resistance in both species . This genome‐derived hypothesis that altered LPS modification underlies resistance was ultimately confirmed for both organisms by comparing LPS modifications in susceptible and resistant isolates …”

Section: Evolution Of Antibiotic Resistancementioning

confidence: 93%

“…Interestingly, in both K. pneumoniae and A. baumannii , genomic sequencing studies have found mutations in a common regulatory pathway controlling LPS modification systems, indicating that LPS modification is key to resistance in both species . This genome‐derived hypothesis that altered LPS modification underlies resistance was ultimately confirmed for both organisms by comparing LPS modifications in susceptible and resistant isolates …”

Section: Evolution Of Antibiotic Resistancementioning

confidence: 95%

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Genomic epidemiology of multidrug‐resistant Gram‐negative organisms

Hawken

Snitkin

2018

Annals of the New York Academy of Sciences

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The emergence and spread of antibiotic-resistant Gram-negative bacteria (rGNB) across global healthcare networks presents a significant threat to public health. As the number of effective antibiotics available to treat these resistant organisms dwindles, it is essential that we devise more effective strategies for controlling their proliferation. Recently, whole-genome sequencing has emerged as a disruptive technology that has transformed our understanding of the evolution and epidemiology of diverse rGNB species, and it has the potential to guide strategies for controlling the evolution and spread of resistance. Here, we review specific areas in which genomics has already made a significant impact, including outbreak investigations, regional epidemiology, clinical diagnostics, resistance evolution, and the study of epidemic lineages. While highlighting early successes, we also point to the next steps needed to translate this technology into strategies to improve public health and clinical medicine.

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Section: Mutational Modes Of Resistancementioning

confidence: 90%

Section: Mutational Modes Of Resistancementioning

confidence: 90%

Section: Evolution Of Antibiotic Resistancementioning

confidence: 93%

Section: Evolution Of Antibiotic Resistancementioning

confidence: 95%

See 2 more Smart Citations

Genomic epidemiology of multidrug‐resistant Gram‐negative organisms

Hawken

Snitkin

2018

Annals of the New York Academy of Sciences

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“…The colistin-resistant K. pneumoniae strains have altered LPS structures that limit the binding of the drug to the bacterial membrane [97]. Recent characterization of LPS from infected patients showed the rapid acquisition of genomic- and plasmid-mediated mutations, leading to alterations in the composition of lipid A and colistin resistance [98]. Perhaps the most concerning of these genetic elements is the emergence of the mobilized colistin resistance ( mcr-1 ), a mobile plasmid rapidly shared amongst all members of the Enterobacteriaceae [99].…”

Section: Surface Properties Of K Pneumoniae and Immune Recognitionmentioning

confidence: 99%

Pseudomonas aeruginosa and Klebsiella pneumoniae Adaptation to Innate Immune Clearance Mechanisms in the Lung

Riquelme¹,

Ahn²,

Prince³

2018

J Innate Immun

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Many different species of gram-negative bacteria are associated with infection in the lung, causing exacerbations of chronic obstructive pulmonary disease, cystic fibrosis (CF), and ventilator-associated pneumonias. These airway pathogens must adapt to common host clearance mechanisms that include killing by antimicrobial peptides, antibiotics, oxidative stress, and phagocytosis by leukocytes. Bacterial adaptation to the host is often evident phenotypically, with increased extracellular polysaccharide production characteristic of some biofilm-associated organisms. Given the relatively limited repertoire of bacterial strategies to elude airway defenses, it seems likely that organisms sharing the same ecological niche might also share common strategies to persistently infect the lung. In this review, we will highlight some of the major factors responsible for the adaptation of Pseudomonas aeruginosa to the lung, addressing how growth in biofilms enables persistent infection, relevant to, but not limited to, the pathogenesis of infection in CF. In contrast, we will discuss how carbapenem-resistant Klebsiella pneumoniae evade immune clearance, an organism often associated with ventilator-associated pneumonia and health-care-acquired pneumonias, but not a typical pathogen in CF.

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Analysis of carbohydrates and glycoconjugates by matrix‐assisted laser desorption/ionization mass spectrometry: An update for 2017–2018

Harvey

2021

Mass Spectrometry Reviews

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This review is the tenth update of the original article published in 1999 on the application of matrix‐assisted laser desorption/ionization mass spectrometry (MALDI) mass spectrometry to the analysis of carbohydrates and glycoconjugates and brings coverage of the literature to the end of 2018. Also included are papers that describe methods appropriate to glycan and glycoprotein analysis by MALDI, such as sample preparation techniques, even though the ionization method is not MALDI. Topics covered in the first part of the review include general aspects such as theory of the MALDI process, new methods, matrices, derivatization, MALDI imaging, fragmentation and the use of arrays. The second part of the review is devoted to applications to various structural types such as oligo‐ and poly‐saccharides, glycoproteins, glycolipids, glycosides, and biopharmaceuticals. Most of the applications are presented in tabular form. The third part of the review covers medical and industrial applications of the technique, studies of enzyme reactions, and applications to chemical synthesis. The reported work shows increasing use of combined new techniques such as ion mobility and highlights the impact that MALDI imaging is having across a range of diciplines. MALDI is still an ideal technique for carbohydrate analysis and advancements in the technique and the range of applications continue steady progress.

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Structural modification of LPS in colistin-resistant, KPC-producing Klebsiella pneumoniae

Abstract: The pathway to colistin resistance in K. pneumoniae primarily involves lipid A modification with Ara4N in clinical settings.

Cited by 70 publications

References 28 publications

Genomic epidemiology of multidrug‐resistant Gram‐negative organisms

Genomic epidemiology of multidrug‐resistant Gram‐negative organisms

<b><i>Pseudomonas aeruginosa</i></b> and <b><i>Klebsiella</i></b> <b><i>pneumoniae</i></b> Adaptation to Innate Immune Clearance Mechanisms in the Lung

Analysis of carbohydrates and glycoconjugates by matrix‐assisted laser desorption/ionization mass spectrometry: An update for 2017–2018

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