A molecular overview of the polymyxin-LPS interaction in the context of its mode of action and resistance development

Padhy, Indira; Dwibedy, Sambit K.; Mohapatra, Saswat S.

doi:10.1016/j.micres.2024.127679

Cited by 8 publications

(5 citation statements)

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“…As far as mechanisms of Col R development are concerned, primarily the loss-of-function mutations in the genes encoding bacterial TCS systems and their regulons involved in outer membrane remodelling are implicated [1]. Moreover, the spread of plasmid-borne mcr genes has a significant role in the rapid emergence of Col R [9].…”

Section: Discussionmentioning

confidence: 99%

“…[1]. Moreover, resistance can also arise by spontaneous mutations in the genes encoding bacterial two-component signalling systems (TCSs) involved in membrane remodelling [1]. However, a major factor driving the global rise of Col R is the plasmid-mediated mcr (mobile colistin resistance) gene, first reported in China in 2015 [8].…”

Section: Intrinsic Resistance To Polymyxins Is Exhibited By a Variety...mentioning

confidence: 99%

“…Increasing incidences of Col R among the GNB species such as Escherichia coli , Klebsiella pneumonia , Pseudomonas aeruginosa , and Acinetobacter baumannii responsible for hospital-acquired (nosocomial) infections are reported from across the globe [1]. This has posed a formidable challenge in the healthcare sector due to the limited therapeutic alternatives available.…”

Section: Introductionmentioning

confidence: 99%

“…The rise and spread of antibiotic-resistant bacterial pathogens, specifically of the Gram-negative type, is one of the foremost challenges in the healthcare sector. Colistin, the cationic lipopeptide antibiotic of the polymyxin class functions by targeting the outer membrane of Gram-negative bacteria (GNB) and is used as a last option antibiotic against them [1]. Colistin is also used in animal feed, and poultry farms for prophylactic reasons.…”

Section: Introductionmentioning

confidence: 99%

“…Intrinsic resistance to polymyxins is exhibited by a variety of GNB species such as Morganella morganii , Proteus mirabilis , Aeromonas hydrophilia, Burkholderia cepacia , Serratia marcescens, etc. [1]. Moreover, resistance can also arise by spontaneous mutations in the genes encoding bacterial two-component signalling systems (TCSs) involved in membrane remodelling [1].…”

Section: Introductionmentioning

confidence: 99%

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Colistin resistance among the Gram-negative nosocomial pathogens in India: A systematic review and meta-analysis

Dwibedy,

Padhy,

Panda

et al. 2024

Preprint

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Background The rapid rise of nosocomial infections and the growing ineffectiveness of frontline antibiotics against Gram-negative bacteria (GNB) have put the healthcare sector under unprecedented stress. In this scenario, colistin, an antibiotic of the polymyxin class, has become the last resort treatment option. The unrestricted use of colistin in the preceding decades has led to the emergence of colistin-resistant (ColR) bacterial strains. Unfortunately, comprehensive data on the prevalence of ColR nosocomial pathogens in India are lacking. This study was conducted to address this information gap and to determine the prevalence of ColR among the nosocomial GNB species in India. Methods A systematic review and meta-analysis were conducted to determine the prevalence of ColR among the nosocomial GNB species in India and their geographical distribution. A systematic search of the online databases was performed and eligible studies meeting the inclusion criteria were used for qualitative synthesis. The combined event rate and 95% confidence interval were estimated using forest plot with a random-effect model. Cochrane Q statistics and I2 statistics were used to detect possible heterogeneity. Results From a total of 1865 retrieved records from 4 databases, 36 studies were included in the study. Among the most common nosocomial pathogens, K. pneumoniae showed a rate of ColR at 17.4%, followed by P. aeruginosa (14.1%), E. coli (12.3%), and A. baumannii (12.2%). Interestingly, our analysis revealed that E. cloacae has the highest rate of ColR at 28.5%. Conclusions The level of resistance displayed by K. pneumoniae, P. aeruginosa, and to a lesser extent, E. coli and A. baumannii in the Indian subcontinent poses a challenge for public health management. Though prevalence may differ among regions and over time, continued surveillance, and efforts to curb the spread of resistance are crucial to ensure the continued effectiveness of this critical antibiotic.

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Section: Discussionmentioning

confidence: 99%