Planet PJ

References (5)

Title : Structure-guided microbial targeting of antistaphylococcal prodrugs - Miller_2021_Elife_10_e66657
Author(s) : Miller JJ , Shah IT , Hatten J , Barekatain Y , Mueller EA , Moustafa AM , Edwards RL , Dowd CS , Hoops GC , Johnson RJ , Planet PJ , Muller FL , Jez JM , Odom John AR
Ref : Elife , 10 : , 2021
Abstract : Carboxy ester prodrugs are widely employed to increase oral absorption and potency of phosphonate antibiotics. Prodrugging can mask problematic chemical features that prevent cellular uptake and may enable tissue-specific compound delivery. However, many carboxy ester promoieties are rapidly hydrolyzed by serum esterases, limiting their therapeutic potential. While carboxy ester-based prodrug targeting is feasible, it has seen limited use in microbes as microbial esterase-specific promoieties have not been described. Here we identify the bacterial esterases, GloB and FrmB, that activate carboxy ester prodrugs in Staphylococcus aureus. Additionally, we determine the substrate specificities for FrmB and GloB and demonstrate the structural basis of these preferences. Finally, we establish the carboxy ester substrate specificities of human and mouse sera, ultimately identifying several promoieties likely to be serum esterase-resistant and microbially labile. These studies will enable structure-guided design of antistaphylococcal promoieties and expand the range of molecules to target staphylococcal pathogens.
ESTHER : Miller_2021_Elife_10_e66657
PubMedSearch : Miller_2021_Elife_10_e66657
PubMedID: 34279224
Gene_locus related to this paper: staau-SA2422

Title : Evolution of hypervirulence by a MRSA clone through acquisition of a transposable element - Benson_2014_Mol.Microbiol_93_664
Author(s) : Benson MA , Ohneck EA , Ryan C , Alonzo F, 3rd , Smith H , Narechania A , Kolokotronis SO , Satola SW , Uhlemann AC , Sebra R , Deikus G , Shopsin B , Planet PJ , Torres VJ
Ref : Molecular Microbiology , 93 :664 , 2014
Abstract : Staphylococcus aureus has evolved as a pathogen that causes a range of diseases in humans. There are two dominant modes of evolution thought to explain most of the virulence differences between strains. First, virulence genes may be acquired from other organisms. Second, mutations may cause changes in the regulation and expression of genes. Here we describe an evolutionary event in which transposition of an IS element has a direct impact on virulence gene regulation resulting in hypervirulence. Whole-genome analysis of a methicillin-resistant S. aureus (MRSA) strain USA500 revealed acquisition of a transposable element (IS256) that is absent from close relatives of this strain. Of the multiple copies of IS256 found in the USA500 genome, one was inserted in the promoter sequence of repressor of toxins (Rot), a master transcriptional regulator responsible for the expression of virulence factors in S. aureus. We show that insertion into the rot promoter by IS256 results in the derepression of cytotoxin expression and increased virulence. Taken together, this work provides new insight into evolutionary strategies by which S. aureus is able to modify its virulence properties and demonstrates a novel mechanism by which horizontal gene transfer directly impacts virulence through altering toxin regulation.
ESTHER : Benson_2014_Mol.Microbiol_93_664
PubMedSearch : Benson_2014_Mol.Microbiol_93_664
PubMedID: 24962815

Title : Genome Sequence of Bacterial Interference Strain Staphylococcus aureus 502A - Parker_2014_Genome.Announc_2_e00284
Author(s) : Parker D , Narechania A , Sebra R , Deikus G , Larussa S , Ryan C , Smith H , Prince A , Mathema B , Ratner AJ , Kreiswirth B , Planet PJ
Ref : Genome Announc , 2 : , 2014
Abstract : Staphylococcus aureus 502A was a strain used in bacterial interference programs during the 1960s and early 1970s. Infants were deliberately colonized with 502A with the goal of preventing colonization with more invasive strains. We present the completed genome sequence of this organism.
ESTHER : Parker_2014_Genome.Announc_2_e00284
PubMedSearch : Parker_2014_Genome.Announc_2_e00284
PubMedID: 24723721

Title : Genome sequence of Aggregatibacter actinomycetemcomitans RHAA1, isolated from a rhesus macaque, an Old World primate - Karched_2012_J.Bacteriol_194_1275
Author(s) : Karched M , Furgang D , Planet PJ , Desalle R , Fine DH
Ref : Journal of Bacteriology , 194 :1275 , 2012
Abstract : Aggregatibacter actinomycetemcomitans is implicated in localized aggressive periodontitis. We report the first genome sequence of an A. actinomycetemcomitans strain isolated from an Old World primate.
ESTHER : Karched_2012_J.Bacteriol_194_1275
PubMedSearch : Karched_2012_J.Bacteriol_194_1275
PubMedID: 22328766
Gene_locus related to this paper: aggac-g3zaa7 , aggac-h0kcu9

Title : Complete genome sequence of Aggregatibacter (Haemophilus) aphrophilus NJ8700 - Di Bonaventura_2009_J.Bacteriol_191_4693
Author(s) : Di Bonaventura MP , Desalle R , Pop M , Nagarajan N , Figurski DH , Fine DH , Kaplan JB , Planet PJ
Ref : Journal of Bacteriology , 191 :4693 , 2009
Abstract : We report the finished and annotated genome sequence of Aggregatibacter aphrophilus strain NJ8700, a strain isolated from the oral flora of a healthy individual, and discuss characteristics that may affect its dual roles in human health and disease. This strain has a rough appearance, and its genome contains genes encoding a type VI secretion system and several factors that may participate in host colonization.
ESTHER : Di Bonaventura_2009_J.Bacteriol_191_4693
PubMedSearch : Di Bonaventura_2009_J.Bacteriol_191_4693
PubMedID: 19447908
Gene_locus related to this paper: aggan-c6am11 , aggan-c6ams5 , aggan-c6apu1 , aggap-g4bej6