Complete Genome Sequence of the Multiresistant Taxonomic Outlier Pseudomonas aeruginosa PA7

Abstract

Pseudomonas aeruginosa PA7 is a non-respiratory human isolate from Argentina that is multiresistant to antibiotics. We first sequenced gyrA, gyrB, parC, parE, ampC, ampR, and several housekeeping genes and found that PA7 is a taxonomic outlier. We report here the complete sequence of the 6,588,339 bp genome, which has only about 95% overall identity to other strains. PA7 has multiple novel genomic islands and a total of 51 occupied regions of genomic plasticity. These islands include antibiotic resistance genes, parts of transposons, prophages, and a pKLC102-related island. Several PA7 genes not present in PAO1 or PA14 are putative orthologues of other Pseudomonas spp. and Ralstonia spp. genes. PA7 appears to be closely related to the known taxonomic outlier DSM1128 (ATCC9027). PA7 lacks several virulence factors, notably the entire TTSS region corresponding to PA1690-PA1725 of PAO1. It has neither exoS nor exoU and lacks toxA, exoT, and exoY. PA7 is serotype O12 and pyoverdin type II. Preliminary proteomic studies indicate numerous differences with PAO1, some of which are probably a consequence of a frameshift mutation in the mvfR quorum sensing regulatory gene.

Primary mechanisms mediating aminoglycoside resistance in the multidrug-resistant Pseudomonas aeruginosa clinical isolate PA7

“…The complete genome sequence of P. aeruginosa PA7, which exhibits resistance to multiple antibiotics, including amikacin, was recently reported (Roy et al, 2010). The identification of mexXY-oprA (PSPA7_3269-3270-3271), encoding a multidrug efflux pump, and aacC4 (PSPA7_3724.1), encoding an AAC(69)-II, as aminoglycoside resistance determinants from the PA7 genome was very interesting, although there are several other AMEs in the PA7 genome that are not considered to be clinically relevant judging from their putative substrate specificities.…”

“…The identification of mexXY-oprA (PSPA7_3269-3270-3271), encoding a multidrug efflux pump, and aacC4 (PSPA7_3724.1), encoding an AAC(69)-II, as aminoglycoside resistance determinants from the PA7 genome was very interesting, although there are several other AMEs in the PA7 genome that are not considered to be clinically relevant judging from their putative substrate specificities. MexXY-OprA of PA7 is a 'hybrid' system in that the PA7-specific oprA gene that is absent from the other known P. aeruginosa strains such as PAO1, PA14 and LESB58, and is linked to mexXY (Roy et al, 2010). MexX (397 aa) and MexY (1045 aa) of PA7 showed strong sequence similarities to MexXY (www.pseudomonas.…”

“…OprA of B. pseudomallei is an outer membrane component of AmrABOprA, which is a major multidrug efflux pump that is implicated in the pan-aminoglycoside resistance of the organism and is closely related to MexXY of P. aeruginosa (Moore et al, 1999;Mima & Schweizer, 2010). The cognate regulator mexZ (PSPA7_3268) located upstream of mexXYoprA but divergently transcribed in PA7 is intact (Roy et al, 2010). Aac4 of PA7 functions as an AAC(69)-II due to the substitution of a serine for a leucine at position 117 in PSPA7_3724.1 (Roy et al, 2010).…”

“…Among the AMEs, AAC(69)-II and ANT(299)-I are the most prevalent mechanisms for aminoglycoside resistance in P. aeruginosa (Armstrong & Miller, 2010;Poole, 2005). RMTs were recently discovered in P. aeruginosa (Yokoyama et al, 2003) and these promote high-level resistance to clinically used aminoglycosides, such as gentamicin, tobramycin and amikacin (Doi & Arakawa, 2007;Doi & Arakawa, 2007;Poole, 2011).The complete genome sequence of P. aeruginosa PA7, which exhibits resistance to multiple antibiotics, including amikacin, was recently reported (Roy et al, 2010). The identification of mexXY-oprA (PSPA7_3269-3270-3271), encoding a multidrug efflux pump, and aacC4 (PSPA7_3724.1), encoding an AAC(69)-II, as aminoglycoside resistance determinants from the PA7 genome was very interesting, although there are several other AMEs in the PA7 genome that are not considered to be clinically relevant judging from their putative substrate specificities.…”

A Pseudomonas aeruginosa TIR effector mediates immune evasion by targeting UBAP1 and TLR adaptors

“…However, in a cystic fibrosis context, colonizing strains modulate levels of expression of some of these virulence factors (Hauser et al , 2011), namely down‐regulation of the T3SS (Jain et al , 2004) and undergo a remarkable accumulation of pathoadaptive mutations (Marvig et al , 2014). The PA7‐related P. aeruginosa strains lack the 20‐Kb‐long genomic region encoding the T3SS core components and all genes encoding secreted effectors but contains several additional genomic islands and potential novel virulence factors (Pirnay et al , 2009; Roy et al , 2010; Cadoret et al , 2014; Freschi et al , 2015). In some of these strains, such as CLJ1, an exolysin secreted by a two‐partner secretion system is responsible for hypervirulence (Elsen et al , 2014).…”