Efflux pump in genomic island GI-M202a mediates transfer of Polymyxin B resistance in Pandoraea pnomenusa M202 (preprint)

Background Polymyxin B was thought to be last-line therapeutic options against multidrug-resistant Gram-negative bacteria, especially in COVID-19 co-infections or other serious infections. The risk of antimicrobial resistance and its spread to the environment should be brought to the forefront.Methods P. pnomenusa M202 was isolated under selection with 8 mg/L polymyxin B from hospital sewage. The genome of M202 was sequenced by PacBio RS II and Illumina HiSeq 4000 platforms. MFS transporter recombinant E. coli strain Mrc-3 was constructed by transferring encoding gene FKQ53_RS21695, a gene in Genomic islands (GIs) of M202, to E. coli 25DN. Mating experiments were performed to evaluate transfer of MFS transporter to Escherichia coli 25DN. And influences of efflux pump inhibitors on MICs were determined. The mechanism of polymyxin B excretion mediated by FKQ53_RS21695 was investigated by Discovery Studio 2.0 based on its homologous model.Results MICs of multidrug-resistant bacterial strain P. pnomenusa M202, isolated from hospital sewage, for polymyxin B is 96 mg/L. Genomic Island GI-M202a with major facilitator superfamily (MFS) transporter encoding gene and conjugative transfer proteins encoding genes of type IV secretion system was identified in strain M202. The mating experiment between M202 and Escherichia coli 25DN reflected the transferability of polymyxin B resistant GI-M202a. Efflux pump inhibitor and heterogeneous expression assays also suggested that MFS transporter gene FKQ53_RS21695 in GI-M202a was responsible to polymyxin B resistance. Molecular docking revealed that polymyxin B fatty acyl group insert into hydrophobic region of transmembrane core with Pi-alkyl and unfavorable bump interactions, and then polymyxin B turns over around Tyr43 to left the peptide group to outside during efflux process, accompanies with conformation change of MFS transporter from inward to outward. Additionally, verapamil and CCCP demonstrated significant inhibition by competing binding sites.Conclusions These findings demonstrated that GI-M202a along with MFS transporter FKQ53_RS21695 in P. pnomenusa M202 could mediate the transmission of polymyxin B resistances.

Case Report: Effects of Sars-CoV-2 on Marfan syndrome with resulting acute aortic dissection.

Marfan syndrome is one of the most common inherited connective tissue disorders that affects the heart, eyes, blood vessels, and bones. It occurs in approximately 1-2 per 10,000 individuals annually. Many patients with Marfan syndrome eventually develop aortic wall abnormalities, often resulting in aortic dilatation, which increases the risk of acute aortic dissection. Recent studies involving SARS-CoV-2 propose that individuals with connective tissue disorders such as Marfan syndrome can have additional associated conditions that could impose a higher risk for morbidity and mortality from SARS-CoV-2. The purpose of this article is to discuss the interrelationship between Marfan Syndrome, Acute Type A Aortic Dissection in a patient with Sars-CoV-2 infection. Pertinent review of these conditions, diagnostic findings, treatment, and the patient's clinical course will be discussed. There is minimal research focused on the connection between this novel virus, Marfan Syndrome, and compounding risk for aortic dissection.

Late onset sclerotomy dehiscence in a patient with Marfan syndrome presenting as recurrent episodes of raised intraocular pressure.

A man in his 50s presented to the eye emergency department on three separate occasions complaining of blurred vision and discomfort in the left eye. He had a history of Marfan syndrome and had undergone bilateral 20-gauge (G) pars plana vitrectomy and lensectomy 20 years prior for ectopia lentis. On examination he had epithelial corneal oedema, raised intraocular pressure >40 mm Hg and conjunctival chemosis, which later appeared as a bleb-like conjunctival elevation. Acute treatment with oral acetazolamide and topical ocular hypotensive agents produced a marked reduction in intraocular pressure to 2-4 mm Hg. A presumed diagnosis of a leaking scleral wound was made. He underwent scleral exploration under general anaesthesia and a leaking sclerotomy was uncovered. The defect was repaired successfully using a scleral patch graft. Late dehiscence of a sclerotomy has been reported rarely in patients with Marfan syndrome. This is the first reported case to present atypically with intermittent episodes of raised intraocular pressure rather than with hypotony.

Acute complicated type B aortic dissection during the New York City COVID-19 surge.

The impact of the coronavirus disease 2019 (COVID-19) pandemic in New York City (NYC) is dramatic. COVID-19 cases surged, hospitals expanded to meet capacity, and NYC remains the global epicenter of this pandemic. During this unprecedented time, a young woman with known Marfan syndrome presented with an acute complicated type B aortic dissection to our Aortic Center. Using the provisional extension to induce a complete attachment technique, we treated this patient and quickly discharged her the next day to decrease the risk of COVID-19 infection. Her progress was monitored using frequent phone calls and one office visit at two weeks.