On the mechanism of solute uptake in Pseudomonas

Hancock, Robert E. W.

doi:10.2741/1075

Cited by 36 publications

(12 citation statements)

References 66 publications

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“…However, hydrophilic antibiotics can enter cells by diffusing through membrane channels or porin proteins in a non-specific manner. As one of the intrinsic mechanisms, P. aeruginosa limits antibiotic entry by reducing the number of non-specific porin proteins and replacing them with specific or more-selective channels for taking up required nutrients resulting in lowered permeability to toxic chemicals (Tamber and Hancock, 2003 ; Figure 3 ). P. aeruginosa resistance to currently used broad-spectrum drugs such as carbapenems and cephalosporins is commonly caused by this adaptation (El Amin et al, 2005 ; Baumgart et al, 2010 ).…”

Section: Antibiotic Resistance Mechanismsmentioning

confidence: 99%

Pseudomonas aeruginosa Lifestyle: A Paradigm for Adaptation, Survival, and Persistence

Moradali

Ghods

Rehm

2017

Front. Cell. Infect. Microbiol.

1,138

1,016

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Pseudomonas aeruginosa is an opportunistic pathogen affecting immunocompromised patients. It is known as the leading cause of morbidity and mortality in cystic fibrosis (CF) patients and as one of the leading causes of nosocomial infections. Due to a range of mechanisms for adaptation, survival and resistance to multiple classes of antibiotics, infections by P. aeruginosa strains can be life-threatening and it is emerging worldwide as public health threat. This review highlights the diversity of mechanisms by which P. aeruginosa promotes its survival and persistence in various environments and particularly at different stages of pathogenesis. We will review the importance and complexity of regulatory networks and genotypic-phenotypic variations known as adaptive radiation by which P. aeruginosa adjusts physiological processes for adaptation and survival in response to environmental cues and stresses. Accordingly, we will review the central regulatory role of quorum sensing and signaling systems by nucleotide-based second messengers resulting in different lifestyles of P. aeruginosa. Furthermore, various regulatory proteins will be discussed which form a plethora of controlling systems acting at transcriptional level for timely expression of genes enabling rapid responses to external stimuli and unfavorable conditions. Antibiotic resistance is a natural trait for P. aeruginosa and multiple mechanisms underlying different forms of antibiotic resistance will be discussed here. The importance of each mechanism in conferring resistance to various antipseudomonal antibiotics and their prevalence in clinical strains will be described. The underlying principles for acquiring resistance leading pan-drug resistant strains will be summarized. A future outlook emphasizes the need for collaborative international multidisciplinary efforts to translate current knowledge into strategies to prevent and treat P. aeruginosa infections while reducing the rate of antibiotic resistance and avoiding the spreading of resistant strains.

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Section: Antibiotic Resistance Mechanismsmentioning

confidence: 99%

Pseudomonas aeruginosa Lifestyle: A Paradigm for Adaptation, Survival, and Persistence

Moradali

Ghods

Rehm

2017

Front. Cell. Infect. Microbiol.

1,138

1,016

View full text Add to dashboard Cite

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“…By expressing either a generalist multidrug efflux pump 111–114 or an antibiotic-specific exporter, such as tetracycline efflux pumps 115 , bacteria keep the intracellular concentration of the antibiotic below inhibitory levels. Alternatively, some bacteria reduce their cell membrane or cell wall permeability to prevent antibiotics from entering the cell by decreasing porin expression or expressing a more selective porin variant 116,117 . In some cases, bacteria will use several complementary mechanisms to achieve high levels of resistance.…”

Section: Figurementioning

confidence: 99%

Next-generation approaches to understand and combat the antibiotic resistome

2017

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Antibiotic resistance is a natural feature of diverse microbial ecosystems. Although recent studies of the antibiotic resistome have highlighted barriers to the horizontal transfer of antibiotic resistance genes between habitats, the rapid global spread of genes that confer resistance to carbapenem, colistin and quinolone antibiotics illustrates the dire clinical and societal consequences of such events. Over time, the study of antibiotic resistance has grown from focusing on single pathogenic organisms in axenic culture to studying antibiotic resistance in pathogenic, commensal and environmental bacteria at the level of microbial communities. As the study of antibiotic resistance advances, it is important to incorporate this comprehensive approach to better inform global antibiotic resistance surveillance and antibiotic development. It is increasingly becoming apparent that although not all resistance genes are likely to geographically and phylogenetically disseminate, the threat presented by those that are is serious and warrants an interdisciplinary research focus. In this Review, we highlight seminal work in the resistome field, discuss recent advances in the studies of resistomes, and propose a resistome paradigm that can pave the way for the improved proactive identification and mitigation of emerging antibiotic resistance threats.

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“…However, charged solutes such as sodium cations and hydrophilic nutrients such as glucose enter freely into the cytosol once they traverse the OM. Their uptake is achieved through the use of solute-specific energy-dependent transporter proteins (58). Some weakly charged or neutral amphiphilic compounds may also enter the cytosol by utilizing proton motive force (PMF) (59,60).…”

Section: Permeability Is An Important Consideration In Developing Antmentioning

confidence: 99%

Antibiotic Hybrids: the Next Generation of Agents and Adjuvants against Gram-Negative Pathogens?

et al. 2018

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The global incidence of drug-resistant Gram-negative bacillary infections has been increasing, and there is a dire need to develop novel strategies to overcome this problem. Intrinsic resistance in Gram-negative bacteria, such as their protective outer membrane and constitutively overexpressed efflux pumps, is a major survival weapon that renders them refractory to current antibiotics. Several potential avenues to overcome this problem have been at the heart of antibiotic drug discovery in the past few decades. We review some of these strategies, with emphasis on antibiotic hybrids either as stand-alone antibacterial agents or as adjuvants that potentiate a primary antibiotic in Gram-negative bacteria. Antibiotic hybrid is defined in this review as a synthetic construct of two or more pharmacophores belonging to an established agent known to elicit a desired antimicrobial effect. The concepts, advances, and challenges of antibiotic hybrids are elaborated in this article. Moreover, we discuss several antibiotic hybrids that were or are in clinical evaluation. Mechanistic insights into how tobramycin-based antibiotic hybrids are able to potentiate legacy antibiotics in multidrug-resistant Gram-negative bacilli are also highlighted. Antibiotic hybrids indeed have a promising future as a therapeutic strategy to overcome drug resistance in Gram-negative pathogens and/or expand the usefulness of our current antibiotic arsenal.

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On the mechanism of solute uptake in Pseudomonas

Cited by 36 publications

References 66 publications

Pseudomonas aeruginosa Lifestyle: A Paradigm for Adaptation, Survival, and Persistence

Pseudomonas aeruginosa Lifestyle: A Paradigm for Adaptation, Survival, and Persistence

Next-generation approaches to understand and combat the antibiotic resistome

Antibiotic Hybrids: the Next Generation of Agents and Adjuvants against Gram-Negative Pathogens?

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