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Systems-level analysis of NalD mutation, a recurrent driver of rapid drug resistance in acute Pseudomonas aeruginosa infection

Jinyuan Yan, Henri Estanbouli, Chen Liao, Wook Kim, Jonathan M. Monk, Rayees Rahman, Mini Kamboj, Bernhard O. Palsson, Weigang Qiu, Joao B. Xavier, Kiran Raosaheb Patil
2019 PLoS Computational Biology  
Pseudomonas aeruginosa, a main cause of human infection, can gain resistance to the antibiotic aztreonam through a mutation in NalD, a transcriptional repressor of cellular efflux.  ...  A detailed analysis of one patient's timeline shows how this mutation can emerge in vivo and drive rapid evolution of resistance while the patient received cancer treatment, a bone marrow transplantation  ...  NalD variation linked to multi-drug resistance Our data suggests that NalD is a recurrent driver for aztreonam resistance in P. aeruginosa acute infection.  ... 
doi:10.1371/journal.pcbi.1007562 pmid:31860667 pmcid:PMC6944390 fatcat:cuxr6zxzuzffnihgza722bifbe

Epidemiology and Treatment of Multidrug-Resistant and Extensively Drug-Resistant Pseudomonas aeruginosa Infections

Juan P. Horcajada, Milagro Montero, Antonio Oliver, Luisa Sorlí, Sònia Luque, Silvia Gómez-Zorrilla, Natividad Benito, Santiago Grau
2019 Clinical Microbiology Reviews  
SUMMARY In recent years, the worldwide spread of the so-called high-risk clones of multidrug-resistant or extensively drug-resistant (MDR/XDR) Pseudomonas aeruginosa has become a public health threat.  ...  A section is devoted to reviewing upcoming active drugs such as imipenem-relebactam, cefepime-zidebactam, cefiderocol, and murepavadin.  ...  Apart from its role in intrinsic aminoglycoside resistance, mutation-driven hyperproduction of MexXY is a common driver of resistance to cefepime in clinical strains (39) .  ... 
doi:10.1128/cmr.00031-19 pmid:31462403 pmcid:PMC6730496 fatcat:xgmudhsk75a65pdghttfbptamq

An atlas of the binding specificities of transcription factors in Pseudomonas aeruginosa directs prediction of novel regulators in virulence

Tingting Wang, Wenju Sun, Ligang Fan, Canfeng Hua, Nan Wu, Shaorong Fan, Jilin Zhang, Xin Deng, Jian Yan
2021 eLife  
A high-throughput systematic evolution of ligands by exponential enrichment assay was applied to 371 putative TFs in P. aeruginosa, which resulted in the robust enrichment of 199 sequence motifs describing  ...  To further explore and delineate the physiological and pathogenic roles of TFs in P. aeruginosa, we constructed regulatory networks for nine major virulence-associated pathways, and found that 51 TFs were  ...  ., Systems-level analysis of NalD mutation, a recurrent driver of rapid drug 862 resistance in acute Pseudomonas aeruginosa infection. PLoS Comput Biol 15, e1007562 863 (2019). 864 92. G.  ... 
doi:10.7554/elife.61885 pmid:33779544 pmcid:PMC8041468 fatcat:bl4uvqo5i5e3bdwsleuxv7nipu

Exploring the Effects of Inhaled Antibiotics on the Cystic Fibrosis Lung Microbiome and Pseudomonas aeruginosa Population Diversity and their Clinical Implications [article]

Alya Heirali, University Of Calgary, Michael D. Parkins, Douglas G. Storey
The work presented herein shows that the home environment may serve as a reservoir for infection in patients with CF.  ...  As patients age and disease progression occurs the diversity of organisms colonizing the lower airways generally decreases and patients become dominated by organisms such as Pseudomonas aeruginosa.  ...  Recurrent mutations in different strains occurred in ftsl, the gene encoding penicillin binding protein 3 (PBP3) and negative regulators of the mexAB-oprM efflux system including mexR, nalD and nalC mutations  ... 
doi:10.11575/prism/37484 fatcat:nrppijhsbbcgjirtdy3iqutaqy