Accession ARO:3000149
CARD Short NameFosA
DefinitionAn enzyme that confers resistance to fosfomycin in Serratia marcescens by breaking the epoxide ring of the molecule. It depends on the cofactors Manganese (II) and Potassium and uses Glutathione (GSH) as the nucleophilic molecule. In Pseudomonas aeruginosa, FosA catalyzes the conjugation of glutathione to carbon-1 of fosfomycin, rendering it ineffective as an antibacterial drug.
AMR Gene Familyfosfomycin thiol transferase
Drug Classphosphonic acid antibiotic
Resistance Mechanismantibiotic inactivation
Resistomes with Perfect MatchesPseudomonas aeruginosag+p+wgs
Resistomes with Sequence VariantsPseudomonas aeruginosag+p+wgs, Pseudomonas chlororaphiswgs, Pseudomonas fluorescensg+wgs, Pseudomonas koreensisg+wgs, Pseudomonas putidawgs, Pseudomonas syringaeg+wgs
Classification10 ontology terms | Show
Parent Term(s)2 ontology terms | Show
+ confers_resistance_to_antibiotic fosfomycin [Antibiotic]
+ fosfomycin thiol transferase [AMR Gene Family]
Sub-Term(s)
3 ontology terms | Show
+ phosphonoformate [Adjuvant] is_small_molecule_inhibitor
+ phosphonoacetate [Adjuvant] is_small_molecule_inhibitor
+ acetylphosphonate [Adjuvant] is_small_molecule_inhibitor
Publications

Pakhomova S, et al. 2004. Protein Sci 13(5): 1260-1265. Structure of fosfomycin resistance protein FosA from transposon Tn2921. (PMID 15075406)

Beharry Z, et al. 2005. J. Biol. Chem. 280(18):17786-91 Functional analysis of active site residues of the fosfomycin resistance enzyme FosA from Pseudomonas aeruginosa. (PMID 15741169)

Resistomes

Prevalence of FosA among the sequenced genomes, plasmids, and whole-genome shotgun assemblies available at NCBI or IslandViewer for 413 important pathogens (see methodological details and complete list of analyzed pathogens). Values reflect percentage of genomes, plasmids, genome islands, or whole-genome shotgun assemblies that have at least one hit to the AMR detection model. Default view includes percentages calculated based on Perfect plus Strict RGI hits. Select the checkbox to view percentages based on only Perfect matches to AMR reference sequences curated in CARD (note: this excludes resistance via mutation as references in protein variant models are often wild-type, sensitive sequences).

Prevalence: protein homolog model (view sequences)

SpeciesNCBI ChromosomeNCBI PlasmidNCBI WGSNCBI GI
Pseudomonas aeruginosa99.08%0.29%67.57%0%
Pseudomonas chlororaphis0%0%3.23%0%
Pseudomonas fluorescens27.78%0%9.13%0%
Pseudomonas koreensis75%0%56.52%0%
Pseudomonas putida0%0%1.07%0%
Pseudomonas syringae2.08%0%0.34%0%
Show Perfect Only


Detection Models

Model Type: protein homolog model

Model Definition: Protein Homolog Models (PHM) detect protein sequences based on their similarity to a curated reference sequence, using curated BLASTP bitscore cut-offs. Protein Homolog Models apply to all genes that confer resistance through their presence in an organism, such as the presence of a beta-lactamase gene on a plasmid. PHMs include a reference sequence and a bitscore cut-off for detection using BLASTP. A Perfect RGI match is 100% identical to the reference protein sequence along its entire length, a Strict RGI match is not identical but the bit-score of the matched sequence is greater than the curated BLASTP bit-score cutoff, Loose RGI matches have a bit-score less than the curated BLASTP bit-score cut-off.

Bit-score Cut-off (blastP): 200


>gb|AAG04518.1|+|FosA [Pseudomonas aeruginosa PAO1]
MLTGLNHLTLAVADLPASIAFYRDLLGFRLEARWDQGAYLELGSLWLCLSREPQYGGPAADYTHYAFGIAAADFARFAAQLRAHGVREWK
QNRSEGDSFYFLDPDGHRLEAHVGDLRSRLAACRQAPYAGMRFAD


>gb|AE004091.2|+|1221691-1222098|FosA [Pseudomonas aeruginosa PAO1]
ATGCTTACCGGTCTCAATCACCTGACCCTGGCGGTCGCCGACCTGCCGGCCAGCATCGCCTTCTACCGCGATCTTCTCGGCTTTCGCCTG
GAAGCGCGCTGGGACCAGGGCGCCTATCTCGAACTGGGTTCGCTGTGGCTGTGCCTGTCCCGGGAGCCGCAGTACGGCGGGCCGGCCGCG
GACTACACGCACTACGCCTTCGGCATCGCCGCCGCGGATTTCGCCCGCTTCGCCGCGCAGCTGCGCGCGCATGGCGTGCGCGAATGGAAG
CAGAACCGCAGCGAGGGCGATTCGTTCTACTTCCTCGACCCGGACGGCCATCGCCTGGAGGCCCACGTCGGCGACCTGCGCAGCCGGCTC
GCGGCGTGCCGGCAAGCGCCCTATGCGGGAATGCGTTTCGCCGACTAG