Staphylococcus aureus is a leading cause of both community- and hospital-acquired infections that are increasingly antibiotic resistant. The emergence of S. aureus resistance to even last-line antibiotics heightens the need for the development of new drugs with novel targets. We generated a highly saturated transposon insertion mutant library in the genome of S. aureus and used Tn-seq analysis to probe the entire genome, with unprecedented resolution and sensitivity, for genes of importance in infection. We further identified genes contributing to fitness in various infected compartments (blood and ocular fluids) and compared them to genes required for growth in rich medium. This resulted in the identification of 426 genes that were important for S. aureus fitness during growth in infection models, including 71 genes that could be considered essential for survival specifically during infection. These findings highlight novel as well as previously known genes encoding virulence traits and metabolic pathways important for S. aureus proliferation at sites of infection, which may represent new therapeutic targets.

Staphylococcus aureus contains two distinct teichoic acid (TA) polymers, lipoteichoic acid (LTA) and wall teichoic acid (WTA), which are proposed to play redundant roles in regulating cell division. To gain insight into the underlying biology of S. aureus TAs, we used a small molecule inhibitor to screen a highly saturated transposon library for cellular factors that become essential when WTA is depleted. We constructed an interaction network connecting WTAs with genes involved in LTA synthesis, peptidoglycan synthesis, surface protein display, and D-alanine cell envelope modifications. Although LTAs and WTAs are synthetically lethal, we report that they do not have the same synthetic interactions with other cell envelope genes. For example, D-alanylation, a tailoring modification of both WTAs and LTAs, becomes essential when the former, but not the latter, are removed. Therefore, D-alanine-tailored LTAs are required for survival when WTAs are absent. Examination of terminal phenotoypes led to the unexpected discovery that cells lacking both LTAs and WTAs lose their ability to form Z rings and can no longer divide. We have concluded that the presence of either LTAs or WTAs on the cell surface is required for initiation of S. aureus cell division, but these polymers act as part of distinct cellular networks.synthetic lethality | TraDIS | Tn-seq

Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common form of ischemic optic neuropathy and the second most common optic neuropathy. Patients are generally over the age of 50 years with vasculopathic risk factors (eg, diabetes mellitus, hypertension, and obstructive sleep apnea). The exact mechanism of NAION is not fully understood. In addition, several treatment options have been proposed. This article summarizes the current literature on the diagnosis, treatment, and management of NAION.

PurposeThe purpose of this study was to evaluate intravitreal methotrexate infusion (IMI) during pars plana vitrectomy (PPV) for retinal detachment in patients with high risk for the development of proliferative vitreoretinopathy (PVR).MethodsPatients presenting with severe recurrent PVR with tractional retinal detachment and/or a history of severe ocular inflammation were treated with IMI. Clinical outcomes were determined from a retrospective medical chart review.ResultsTwenty-nine eyes presenting with either tractional retinal detachment and recurrent PVR (n=22) or a history of severe inflammation associated with high PVR risk (n=7) received IMI during PPV. Best-corrected visual acuity at 6 months was ≥20/200 in 19 of 29 eyes (66%) and remained stable or improved compared with initial presentation in 24 of 29 eyes (83%). At the last follow-up examination, the retinas of 26 of 29 eyes (90%) remained attached after IMI while three eyes required another reattachment procedure. Three additional eyes (10%) developed recurrent limited PVR without recurrent RD and were observed. No complications attributable to IMI occurred during a mean follow-up of 27 months.ConclusionEyes at high risk for PVR development due to a history of prior PVR or intraocular inflammation had a low incidence of PVR following IMI at the time of PPV for RD repair. No significant safety issues from IMI were observed in this series.