Polymyxins: To Combine or Not to Combine?

Pérez, Federico; Chakhtoura, Nadim G. El; Yasmin, Mohamad; Bonomo, Robert A.

doi:10.3390/antibiotics8020038

Cited by 37 publications

(32 citation statements)

References 60 publications

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“…Another polymyxin resistance mechanism in K. pneumoniae is the overproduction of the surface anionic capsular polysaccharides (CPS) [23] that represent a protective barrier against polymyxins, where the upregulation of capsular biosynthesis genes, namely; siaD, OmpA, and cps operon (wca), hinders the binding of polymyxins with lipid A [18] by trapping polymyxins [40]. Fresno et al [41] reported that the association between the surface CPS and the LPS is mediated through an ionic interaction that is stabilized by divalent cations.…”

Section: Examples Of Chromosomally Encoding Colistin Resistance Amongmentioning

confidence: 99%

“…Several studies have reported that mutations in PmrB, PhoQ, ParR, and ParS proteins in clinical P. aeruginosa isolates, cause the constitutive overexpression of the LPS modification operon pmrHFIJKLM via the activation of one of the components of the TCSs (PmrB, ParS, ParR) or the inactivation of sensor kinase PhoQ, which acts as a repressor of PhoP activity, thus allowing the PhoP to stimulate pmrHFIJKLM operon expression, leading to the addition of L -Ara4N to the LPS, which, in turn, causes different degrees of colistin resistance [40,54].…”

Section: P Aeruginosamentioning

confidence: 99%

“…Furthermore, in the presence of reduced levels of the cell envelope Mg 2+ , the outer membrane protein OprH (or H1) is overexpressed and binds to the negatively charged phosphate groups, and thus hinders the polymyxin binding and develops polymyxin resistance in P. aeruginosa [16,18,40]. Besides, it has been reported that the down-regulation of porin (OprD) can affect the polymyxins resistance in P. aeruginosa [18].…”

Section: P Aeruginosamentioning

confidence: 99%

“…Besides, it has been reported that the down-regulation of porin (OprD) can affect the polymyxins resistance in P. aeruginosa [18]. Perez et al [40] revealed that polymyxin resistance could also occur via the trapping of polymyxins in the bacterial capsule of P. aeruginosa.…”

Section: P Aeruginosamentioning

confidence: 99%

“…In K. pneumoniae, polymyxin resistance can also occur via the activation of the efflux pumps AcrAB [23,40]. Indeed, efflux pump systems associated with colistin resistance have not been well studied.…”

Section: Efflux Pumpsmentioning

confidence: 99%

See 4 more Smart Citations

Colistin and its role in the Era of antibiotic resistance: an extended review (2000–2019)

Ahmed

Zhong

Cong

et al. 2020

Emerging Microbes & Infections

431

383

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Increasing antibiotic resistance in multidrug-resistant (MDR) Gram-negative bacteria (MDR-GNB) presents significant health problems worldwide, since the vital available and effective antibiotics, including; broad-spectrum penicillins, fluoroquinolones, aminoglycosides, and β-lactams, such as; carbapenems, monobactam, and cephalosporins; often fail to fight MDR Gram-negative pathogens as well as the absence of new antibiotics that can defeat these "superbugs". All of these has prompted the reconsideration of old drugs such as polymyxins that were reckoned too toxic for clinical use. Only two polymyxins, polymyxin E (colistin) and polymyxin B, are currently commercially available. Colistin has re-emerged as a last-hope treatment in the mid-1990s against MDR Gram-negative pathogens due to the development of extensively drug-resistant GNB. Unfortunately, rapid global resistance towards colistin has emerged following its resurgence. Different mechanisms of colistin resistance have been characterized, including intrinsic, mutational, and transferable mechanisms. In this review, we intend to discuss the progress over the last two decades in understanding the alternative colistin mechanisms of action and different strategies used by bacteria to develop resistance against colistin, besides providing an update about what is previously recognized and what is novel concerning colistin resistance.

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Section: Examples Of Chromosomally Encoding Colistin Resistance Amongmentioning

confidence: 99%

Section: P Aeruginosamentioning

confidence: 99%

Section: P Aeruginosamentioning

confidence: 99%

Section: P Aeruginosamentioning

confidence: 99%

Section: Efflux Pumpsmentioning

confidence: 99%

See 3 more Smart Citations

Colistin and its role in the Era of antibiotic resistance: an extended review (2000–2019)

Ahmed

Zhong

Cong

et al. 2020

Emerging Microbes & Infections

431

383

View full text Add to dashboard Cite

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Medicinal Chemistry of β‐Lactam Antibiotics

Testero

Llarrull

Fisher

et al. 2021

Burger's Medicinal Chemistry and Drug Discovery

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The β‐lactam class of antibacterials is a cornerstone of human health. For nearly eight decades, their unparalleled clinical efficacy and clinical safety have made the β‐lactam class preeminent in the treatment of bacterial infection. The relatively brief period in human history during which the β‐lactams have exerted this benefit is a period characterized by continuous medicinal chemistry innovation, seen visibly in the progression from the penicillins to the complex ensemble of β‐lactams (now including also cephalosporins, monobactams, and carbapenems) used in the clinic. The key force behind this innovation is the progressive evolution by bacteria of resistance mechanisms. Today, highly resistant bacteria challenge the way medicinal chemists contemplate the creative alteration of β‐lactam structures, the way the pharmaceutical industry develops β‐lactams (and other antibacterial) structures, and the way the medical community uses antibacterials. This article gives a concise summary of the history of the β‐lactams. Its emphasis is recent structural innovation with respect to the β‐lactams, and with respect to structurally related classes that act to preserve the clinical activity of the β‐lactams through inhibition of bacterial β‐lactam‐hydrolyzing, and thus β‐lactam‐deactivating, enzymes. We integrate these chemistry advances with new biological discoveries with respect to the bactericidal mechanism of the β‐lactams and with respect to bacterial resistance mechanisms. The combination of these perspectives is a foundational perspective to guide the medicinal chemistry future of the β‐lactams.

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Management of Acinetobacter Infections in the Immunosuppressed Host

Baneman

Rana

2020

Emerging Transplant Infections

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Polymyxins: To Combine or Not to Combine?

Cited by 37 publications

References 60 publications

Colistin and its role in the Era of antibiotic resistance: an extended review (2000–2019)

Colistin and its role in the Era of antibiotic resistance: an extended review (2000–2019)

Medicinal Chemistry of β‐Lactam Antibiotics

Management of Acinetobacter Infections in the Immunosuppressed Host

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