Genomics of Aminoglycoside Resistance in Pseudomonas aeruginosa Bloodstream Infections at a United States Academic Hospital

Atassi, Giancarlo; Medernach, Rachel; Scheetz, Marc H.; Nozick, Sophia; Rhodes, Nathaniel J.; Murphy-Belcaster, Megan; Murphy, Katherine R.; Alisoltani, Arghavan; Ozer, Egon A.; Hauser, Alan R.

doi:10.1128/spectrum.05087-22

Cited by 9 publications

(7 citation statements)

References 54 publications

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“…Moreover, these proteins transport a specific range of antimicrobials. For instance, while the MexB efflux pump in P. aeruginosa and the AcrB efflux pump in E. coli do not possess the ability to extrude aminoglycoside antibiotics such as gentamicin and tobramycin, the MexY efflux pump in P. aeruginosa and the AcrD efflux pumps in E. coli are capable of effectively expelling them [ 61 , 73 , 74 ].…”

Section: Rnd Efflux Pumps In P Aeruginosa the Typ...mentioning

confidence: 99%

The Art of War with Pseudomonas aeruginosa: Targeting Mex Efflux Pumps Directly to Strategically Enhance Antipseudomonal Drug Efficacy

Avakh,

Grant,

Cheesman

et al. 2023

Antibiotics

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Pseudomonas aeruginosa (P. aeruginosa) poses a grave clinical challenge due to its multidrug resistance (MDR) phenotype, leading to severe and life-threatening infections. This bacterium exhibits both intrinsic resistance to various antipseudomonal agents and acquired resistance against nearly all available antibiotics, contributing to its MDR phenotype. Multiple mechanisms, including enzyme production, loss of outer membrane proteins, target mutations, and multidrug efflux systems, contribute to its antimicrobial resistance. The clinical importance of addressing MDR in P. aeruginosa is paramount, and one pivotal determinant is the resistance-nodulation-division (RND) family of drug/proton antiporters, notably the Mex efflux pumps. These pumps function as crucial defenders, reinforcing the emergence of extensively drug-resistant (XDR) and pandrug-resistant (PDR) strains, which underscores the urgency of the situation. Overcoming this challenge necessitates the exploration and development of potent efflux pump inhibitors (EPIs) to restore the efficacy of existing antipseudomonal drugs. By effectively countering or bypassing efflux activities, EPIs hold tremendous potential for restoring the antibacterial activity against P. aeruginosa and other Gram-negative pathogens. This review focuses on concurrent MDR, highlighting the clinical significance of efflux pumps, particularly the Mex efflux pumps, in driving MDR. It explores promising EPIs and delves into the structural characteristics of the MexB subunit and its substrate binding sites.

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Section: Rnd Efflux Pumps In P Aeruginosa the Typ...mentioning

confidence: 99%

The Art of War with Pseudomonas aeruginosa: Targeting Mex Efflux Pumps Directly to Strategically Enhance Antipseudomonal Drug Efficacy

Avakh,

Grant,

Cheesman

et al. 2023

Antibiotics

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“…The abovementioned drugs have a relatively high degree of harm to children and are less commonly used in clinical practice ( Lin et al, 2016 ), resulting in a lower resistance rate, which is consistent with the expected results. AMEs genes are associated with resistance to multiple antibiotics ( Atassi et al, 2023 ). Combined with the analysis of genetic testing results, the detection rate of AMEs genes and MexB was high, while the resistance rate of corresponding aminoglycoside antibiotics was 0, which suggests that there may be potential resistance factors, and the relationship between resistance genes and antibiotics needs to be further explored.…”

Section: Discussionmentioning

confidence: 99%

Evaluation and analysis of multidrug resistance- and hypervirulence-associated genes in carbapenem-resistant Pseudomonas aeruginosa strains among children in an area of China for five consecutive years

Zhang,

Zhu,

Gao

et al. 2023

Front. Microbiol.

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IntroductionCarbapenem-resistant Pseudomonas aeruginosa (CRPA) is a growing threat. It is urgent to investigate the multidrug resistance and high virulence of CRPA to provide a basis for infection control and rational use of antibiotics.MethodsA retrospective study of 56 nonduplicated CRPA isolates was conducted.ResultsCRPA mainly came from the intensive care unit (ICU) and was mostly isolated from sputum samples. The carbapenem resistance rates of P. aeruginosa were 21.37% (2016), 10.62, 5.88, 10 and 13.87% from 2016 to 2020, respectively. Carbapenem-resistant enzymes and aminoglycoside-modifying enzyme-encoding genes were detected in all isolates, and extended-spectrum β-lactamase and cephalosporin enzyme-encoding genes were present in 96.43 and 80.38% of isolates, respectively. The detection rate of OprM showed a statistically significant difference (p < 0.05) between the ICU and other wards. Genes related to biofilms, membrane channel proteins, I integrons and efflux systems were detected in all isolates, with detection rates greater than 90%. CRPA was strongly virulent, and over 80% of isolates carried hypervirulence-associated genes (exoU, exoS, exoT, and exoY). The drug resistance rates of cefepime and piperacillin/tazobactam showed a statistically significant difference (p < 0.05) between strains with exoU (+) and exoU (−) (p < 0.05). Notably, out of the 7 individuals who died, 4 had extensively drug-resistant P. aeruginosa (57.14%).DiscussionThe detection rates of various resistance and virulence genes were high, and the coexistence phenomenon was serious. In clinical practice, antibiotics should be used reasonably based on different drug resistance genes to ensure the rationality and safety of patient medication.

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“…Acquired resistance involves the acquisition of a resistance gene or mutation in genes encoding porins, efflux pumps, penicillin-binding proteins, and chromosomal β-lactamase, all contributing to resistance to β-lactams, carbapenems, aminoglycosides, and fluoroquinolones [ 79 ]. P. aeruginosa strains have also been found resistant to aminoglycosides carrying the mexXY genes that induce the modification of aminoglycoside enzymes [ 80 ]. On the other hand, the genes crpP and qnrVC1 have been identified in clinical isolates of P. aeruginosa , which demonstrated resistance to fluoroquinolone [ 81 ].…”

Section: The Abundant Bacteria Implicated In Woundmentioning

confidence: 99%

Biodiversity of Skin Microbiota as an Important Biomarker for Wound Healing

Ersanli,

Tzora,

Voidarou

et al. 2023

Biology

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Cutaneous wound healing is a natural and complex repair process that is implicated within four stages. However, microorganisms (e.g., bacteria) can easily penetrate through the skin tissue from the wound bed, which may lead to disbalance in the skin microbiota. Although commensal and pathogenic bacteria are in equilibrium in normal skin, their imbalance in the wound area can cause the delay or impairment of cutaneous wounds. Moreover, skin microbiota is in constant crosstalk with the immune system and epithelial cells, which has significance for the healing of a wound. Therefore, understanding the major bacteria species in the cutaneous wound as well as their communication with the immune system has gained prominence in a way that allows for the emergence of a new perspective for wound healing. In this review, the major bacteria isolated from skin wounds, the role of the crosstalk between the cutaneous microbiome and immune system to heal wounds, the identification techniques of these bacteria populations, and the applied therapies to manipulate the skin microbiota are investigated.

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Genomics of Aminoglycoside Resistance in Pseudomonas aeruginosa Bloodstream Infections at a United States Academic Hospital

Cited by 9 publications

References 54 publications

The Art of War with Pseudomonas aeruginosa: Targeting Mex Efflux Pumps Directly to Strategically Enhance Antipseudomonal Drug Efficacy

The Art of War with Pseudomonas aeruginosa: Targeting Mex Efflux Pumps Directly to Strategically Enhance Antipseudomonal Drug Efficacy

Evaluation and analysis of multidrug resistance- and hypervirulence-associated genes in carbapenem-resistant Pseudomonas aeruginosa strains among children in an area of China for five consecutive years

Biodiversity of Skin Microbiota as an Important Biomarker for Wound Healing

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