This is a case of a 31-year-old male who was a victim of motor vehicle accident in 2007. He sustained a severe head injury and cervical spine fracture, for which his spine was fixed with a plate and screw, and was intubated for several weeks. His recovery was slow overall, with gradual, mild improvement. Eventually, he became fully conscious and was discharged from hospitalization, although as a paraplegic. The patient sought medical advice over the years for recurrent chest infections, for which he was treated conservatively with antibiotics. Around mid-2016, he was referred to the cardiothoracic unit of our institution as his chest x-ray (CXR) showed a widened mediastinum (Figure 1). The initial laboratory investigations were normal apart from the following parameters: Hemoglobin 11.3 g/dL, hematocrit 35%, Mean corpuscular volume 67.7 fL, mean corpuscular hemoglobin 21.8 pg, albumin 2.7 g/L, creatinine 0.5 mumol/L, Na 135 mmol/L, and erythrocyte sedimentation rate 93 mm/h. Further radiological assessment, computed tomography (CT) of the neck, cervical spine, and chest revealed a superior mediastinal collection with signs of chronic esophageal perforation. The patient underwent a swallowing test and an upper gastroesophageal endoscopy that confirmed the presence of upper esophageal perforation due to erosion of the cervical spine plate and screw into the esophagus. Following a multi-disciplinary discussion represented by neurosurgeons, an otolaryngologist, a thoracic, and a general surgeon, the surgical approach was designed for this case. The patient underwent neck exploration through a cervical incision, the plate was removed, and the perforation was identified. The perforation was repaired using an interposition muscle flap from the strap muscle. A limited thoracotomy revealed extensive pleural adhesions, although no collection was identified. A feeding jejunostomy tube was created through mini-laparotomy, which the patient tolerated well. One week post-operatively, he developed a surgical site infection at the cervical wound. Exploration and drainage were performed along with antimicrobial therapy. This patient had a lengthy post-operative course with several admissions to the intensive care unit (ICU) due to repeated episodes of sepsis. Moreover, he required bronchoscopies and exchanging the tracheostomy. After a few weeks, he developed an acute surgical abdomen for which he underwent exploration and drainage of multiple intra-abdominal abscess collections, from which he recovered. However, he developed persistent status epilepticus over a few months that was difficult to manage. The patient eventually experienced cardiac arrest that could not be revived. The timeline of infections encountered in the patient is illustrated in Figure 2.
An XDR-P. aeruginosa strain (PA179) was repeatedly isolated from the urinary tract of the patient 16 months after his admission, followed by an episode of sepsis during which the same strain was grown from multiple blood culture samples. The identification of suspected P. aeruginosa colonies was confirmed using VITEK MS (BioMerieux, Craponne, France) based on matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) technology with automated broth microdilution (BMD) susceptibility testing using VITEK 2 Software Version 7.01 and AST Card-GN99 (BioMerieux, Craponne, France). Additionally, E tests (AB Biodisk, Solna, Sweden) were used to measure the MIC of two carbapenems, imipenem and meropenem, two beta-lactam/beta-lactamase inhibitor combinations, ceftazidime-avibactam and ceftolozane-tazobactam, and interpreted according to the Clinical and Laboratory Standards Institute (CLSI) 2017 guidelines for all antimicrobials tested. The susceptibility pattern of the blood isolate revealed an extensive drug resistance pattern, as shown in Table 1. 
A range of bioinformatics online tools were used to analyze the sequenced genome including: Soap denovo: de novo draft assembly for the human-sized genomes: (http://soap.genomics.org.cn/soapdenovo.html), Reference-Assisted Genome Ordering Utility (Ragout): (https://github.com/fenderglass/Ragout), Multi-locus sequence typing (MLST): in silico multilocus sequence typing website (http://cge.cbs.dtu.dk/services/), Prokaryotic Genome Annotation Pipeline annotation system (PGAAP): (https://github.com/ncbi/pgap), Rapid Annotation using Subsystem Technology (RAST): (https://rast.nmpdr.org/), Virulence factor database (VFDB) and Virulence factor analyser (VFanalyser): (http://www.mgc.ac.cn/VFs/), PHAge Search Tool (PHAST): (http://phast.wishartlab.com/) and clustered regularly interspaced short palindromic repeats finder (CRISPR): (https://crispr.i2bc.paris-saclay.fr/Server/).
The isolate was subjected to whole genome sequencing as follows: total genomic DNA was prepared using DNeasy blood and tissue kits (Qiagen, Hilden, Germany) according to the manufacturer's recommendations, followed by sequencing using an Illumina HiSeq 4000 system (Illumina, San Diego, CA, USA) at the Beijing Genomics Institute (BGI, Shenzhen, China). Genomic DNA was sheared randomly to construct three read libraries with lengths of 6580692 bp using a Bioruptor ultrasonicator (Diagenode, Denville, NJ, USA) and physicochemical methods. The paired-end fragment libraries were sequenced according to the Illumina HiSeq 4000 system protocol. Low-quality raw reads from paired-end sequencing; those with consecutive bases covered by fewer than five reads were discarded. The sequenced reads were assembled using SOAPdenovo v1.05 software. The complete annotated genome sequences of strain PA179 were deposited in the National Centre for Biotechnology Information (NCBI) and published under the accession number CP058257 (Table 2/Supplementary Table S1). The general genomic features of strain PA179 are summarized in Table 2. Initial assembly using Soap denovo produced 171 scaffolds with 1,88,134 a N50 value and a total sequence length of 69,09,802 bp and coverage of 99.97 x (Supplementary Table S1). Thereafter, it was rearranged to form the complete genome using Ragout (Reference-Assisted Genome Ordering Utility) tool, which resulted in a single contig of size 6580692 bp (Figure 3). In silico analysis of Multi-locus sequence typing (MLST) classified PA179 under the sequence type ST357 (Supplementary Table S1). PGAAP annotation deciphering the PA179 strain revealed that the chromosome comprised 6083 genes, 6023 coding sequences (CDS), 56 tRNA genes, 20 rRNA genes, and 4 non-coding RNAs (Supplementary Table S1). 
With regard to the genomic view of antimicrobial effects, resistance to beta-lactam agents was observed by the presence of blaOXA-10 (J03427), blaOXA-50 (AY306130), blaVEB-9, blaPAO, and the class C beta-lactamase PDC-11. Notably, four Metallo-beta-lactamases (MBL) fold metallo-hydrolase (belonging to Metallo-beta-lactamase super family proteins) were found among the chromosomal gene cluster (WP_003091024.1). Aminoglycoside resistant determinants, namely, aph(3')-IIb, aac(6')-Il (aac(6')-Il_U13880), ant(2' '')-Ia (ant(2'')-Ia_X04555), aac(6')-Il (aac(6')-Il_U13880), ant(2'')-Ia (ant(2'')-Ia_X04555), aac(6')-Il (aac(6')-Il_U13880), ant(2'')-Ia (ant(2''')-Ia_X04555), and aph(3')-IIb_CP006832. The fluoroquinolone-related resistance genes crpP (crpP_HM560971) also existed. Phenicol resistance gene catB7 (AF036933), and tetracycline resistance genes tet(A) (tet(A) (AY196695)) were present (Supplementary Table S2). Additionally, manual examination of RAST output predicted that P. aeruginosa PA179 may contain major efflux pump proteins comprising the RND family of MexCD-OprJ, cobalt efflux protein CorC, multidrug efflux proteins from the MATE family, macrolide-specific efflux protein MacA, and potassium efflux system KefA. Multi-drug resistant efflux pumps of MexX, MexA, and MexE were also detected. (Supplementary Table S1 and S2).
The virulence factor identification VFDB-organized VFanalyser was used to predict the presence of over 222 different virulence factors, including bacteriocins and invasions (Supplementary Table S3). The most remarkable feature of the PA179 genome is the presence of multiple type secretion system proteins. Type 1 (six genes), Type 2 (15 genes), Type 3 (36 genes), Type 4 (20 genes), Type 5 (two genes), and Type 7 (five genes) were identified using both RAST and prokaryotic genome annotation pipeline (PGAAP) annotation system. (Supplementary Table S3). A phage genome with a cluster of genetic rearrangements was observed using PHAST. A total of three phages in the PA197 genome was predicted, from one intact phage, one consisted of an 18.4 kb Pseudomonas phage, NC_030929, with a 62.25% GC content, and 25 CDS were detected. The second phage consisted of a 6.6 kb Pseudomonas phage Pf1 (NC_001331), 62.47% GC content, and eight protein-coding sequences. Furthermore, a partial genome of Pseudomonas phage B3 NC_006548 (19.4 kb region length) was also observed in PA179 with 22 CDS. Prophage visualization and details can be seen in Supplementary Figures 1-4. A total of three CRISPR genes, clustered regularly interspaced short palindromic repeats, were predicted using the CRISPR finder online tool and consisted of sequences ranging from 447 bp to 1047 bp CRISPR size with a 28 bp direct repeat (DR) length. These CRISPR-Cas systems confer flexible, sequence-specific immunity against bacteriophages and mobile genetic elements. (Supplementary Table S4, Supplementary Figures 1-4).
The genomic islands representing mobile elements in the PA179 genome were predicted using the online server "Island Viewer". This was identified in 47 islands in the genome, with several embedded mobile genetic elements. The islands were visualized using Island Viewer software (Figure 4 and Supplementary data Table S5).