Aminoglycoside-Modifying Enzymes Are Sufficient to Make Pseudomonas aeruginosa Clinically Resistant to Key Antibiotics

Thacharodi, Aswin; Lamont, Iain L.

doi:10.3390/antibiotics11070884

Cited by 21 publications

(13 citation statements)

References 92 publications

(106 reference statements)

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“…The genomic sequence analysis of SRS1 and SRS4 also revealed the presence of all 3 classes of Aminoglycoside Modifying Enzymes (AME) i.e., aminoglycoside nucleotidyltransferase (ANT), acetyltransferases (AAC) and phosphotransferase (APHs). The AAC(6")-Ib-cr6 acetyltransferase acetylates not only Tobramycin and Amikacin but also Fluroquinolone antibiotics (Robicsek et al, 2006;Thacharodi and Lamont, 2022). Along with AAC (6")-Ib-4, it is the most abundant type of AAC found in Gramnegative bacteria.…”

Section: Resultsmentioning

confidence: 99%

Genomic Analysis to Elucidate the Antibiotic Resistance Mechanism of Extremely Drug-Resistant Pseudomonas Aeruginosa Strains Isolated From Bangladesh

Zahra

Jabeen

Uddin

et al. 2022

Bioresearch Communications

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Multidrug-resistant P. aeruginosa has potential to cause nosocomial infections. In this study, whole-genome sequencing was performed of two extremely drug-resistant novel strains SRS1 and SRS4 isolated from Bangladesh. The size of draft genome of SRS1 is 6.8 Mbp, and 7.0 Mbp for SRS4. In silico analysis predicted that the genome of SRS1 has 82 and SRS4 has 75 antibiotic-resistant genes (ARGs). Antibiogram results revealed that both SRS1 and SRS4 were resistant to multiple members of the antibiotic groups of β−lactam, quinolones, and aminoglycosides families. In addition, the genomes of both SRS1 and SRS4 were predicted to have multiple mobile elements like prophages and plasmids. Comparative genome analysis with wildtype PAO1 and another drug-resistant P. aeruginosa strain JNQH-PA57 revealed that SRS1 and SRS4 contain more antibiotic resistance genes like AAC (6´)-II, ANT (2´´)-Ia, ANT (3´´)-IIa, OXA-395, PME-1, qacEΔ1, tet(A), tet(D), VEB-9 than PAO1 and JNQH-PA57. This study shows the importance of the genomic study to understand the distribution of ARGs in Bangladeshi P. aeruginosa strains to demonstrate the mechanisms responsible for multi drug resistance. Bioresearch Commu. 9(1): 1208-1214, 2023 (January)

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Section: Resultsmentioning

confidence: 99%

Genomic Analysis to Elucidate the Antibiotic Resistance Mechanism of Extremely Drug-Resistant Pseudomonas Aeruginosa Strains Isolated From Bangladesh

Zahra

Jabeen

Uddin

et al. 2022

Bioresearch Communications

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“…Draft genome assemblies were generated using SPAdes v3.12.0 [ 57 ] with the default settings and the ‘-careful’ option. Remaining genome sequences have been described previously [ 46 , 51 , 53 , 58 , 59 ].…”

Section: Methodsmentioning

confidence: 99%

The PitA protein contributes to colistin susceptibility in Pseudomonas aeruginosa

Erdmann,

Gardner,

Lamont

2023

PLoS ONE

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Pseudomonas aeruginosa is an opportunistic pathogen that causes a wide range of problematic infections in individuals with predisposing conditions. Infections can be treated with colistin but some isolates are resistant to this antibiotic. To better understand the genetic basis of resistance, we experimentally evolved 19 independent resistant mutants from the susceptible laboratory strain PAO1. Whole genome sequencing identified mutations in multiple genes including phoQ and pmrB that have previously been associated with resistance, pitA that encodes a phosphate transporter, and carB and eno that encode enzymes of metabolism. Individual mutations were engineered into the genome of strain PAO1. Mutations in pitA, pmrB and phoQ increased the minimum inhibitory concentration (MIC) for colistin 8-fold, making the bacteria resistant. Engineered pitA/phoQ and pitA/pmrB double mutants had higher MICs than single mutants, demonstrating additive effects on colistin susceptibility. Single carB and eno mutations did not increase the MIC suggesting that their effect is dependent on the presence of other mutations. Many of the resistant mutants had increased susceptibility to β-lactams and lower growth rates than the parental strain demonstrating that colistin resistance can impose a fitness cost. Two hundred and fourteen P. aeruginosa isolates from a range of sources were tested and 18 (7.8%) were colistin resistant. Sequence variants in genes identified by experimental evolution were present in the 18 resistant isolates and may contribute to resistance. Overall our results identify pitA mutations as novel contributors to colistin resistance and demonstrate that resistance can reduce fitness of the bacteria.

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“…P. aeruginosa modifying enzymesaminoglycoside acetyltransferase, aminoglycoside phospho-transfer and aminoglycoside nucleotide transferase catalyse the structural modifications and inactivation of kanamycin, streptomycin and neomycin. 58,59 Outer membrane barrier and efflux mechanism…”

Section: Antibiotic Resistance Mechanism In Pseudomonas Aeruginosamentioning

confidence: 99%

Insights on MDR Mechanism of Pseudomonas aeruginosa with Emphasis on Diabetic Foot Ulcer in the Indian Subcontinent

Chatterjee,

Sivashanmugam

2024

J. Pure Appl. Microbiol.

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Diabetic foot ulcers (DFU) in patients with uncontrolled diabetes mellitus are considered a global public health menace that is highly associated with morbidity and mortality. Pathogenic microorganisms entrenched deep into diabetic foot wounds are the causative agents for delayed healing and escalation of diabetic foot wound severity. Pseudomonas aeruginosa is a common opportunistic pathogen associated with several nosocomial infections, cystic fibrosis, and one of the most critical pathogens often isolated from acute and chronic diabetic foot ulcers. The organism can exhibit resistance to a wide range of antibiotics like ciprofloxacin, cefotaxime, and meropenem, thereby causing severe damage to the host tissues, followed by amputation of the affected foot region. Due to their ability to synthesize biofilms, the wound becomes more chronic and incurable, posing a serious threat to immunocompromised diabetic patients. This review highlights on the insights of pathophysiology and microbiological profile of Diabetic foot ulcers, the resistance mechanisms, and the therapeutics available for dealing with drug-resistant Pseudomonas, which could help clinicians in treating DFUs.

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Aminoglycoside-Modifying Enzymes Are Sufficient to Make Pseudomonas aeruginosa Clinically Resistant to Key Antibiotics

Cited by 21 publications

References 92 publications

Genomic Analysis to Elucidate the Antibiotic Resistance Mechanism of Extremely Drug-Resistant Pseudomonas Aeruginosa Strains Isolated From Bangladesh

Genomic Analysis to Elucidate the Antibiotic Resistance Mechanism of Extremely Drug-Resistant Pseudomonas Aeruginosa Strains Isolated From Bangladesh

The PitA protein contributes to colistin susceptibility in Pseudomonas aeruginosa

Insights on MDR Mechanism of Pseudomonas aeruginosa with Emphasis on Diabetic Foot Ulcer in the Indian Subcontinent

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