(p)ppGpp and CodY Promote Enterococcus faecalis Virulence in a Murine Model of Catheter-Associated Urinary Tract Infection.

In Firmicutes, the nutrient-sensing regulators (p)ppGpp, the effector molecule of the stringent response, and CodY work in tandem to maintain bacterial fitness during infection. Here, we tested (p)ppGpp and codY mutant strains of Enterococcus faecalis in a catheter-associated urinary tract infection (CAUTI) mouse model and used global transcriptional analysis to investigate the relationship of (p)ppGpp and CodY. The absence of (p)ppGpp or single inactivation of codY led to lower bacterial loads in catheterized bladders and diminished biofilm formation on fibrinogen-coated surfaces under in vitro and in vivo conditions. Single inactivation of the bifunctional (p)ppGpp synthetase/hydrolase rel did not affect virulence, supporting previous evidence that the association of (p)ppGpp with enterococcal virulence is not dependent on the activation of the stringent response. Inactivation of codY in the (p)ppGpp0 strain restored E. faecalis virulence in the CAUTI model as well as the ability to form biofilms in vitro Transcriptome analysis revealed that inactivation of codY restores, for the most part, the dysregulated metabolism of (p)ppGpp0 cells. While a clear linkage between (p)ppGpp and CodY with expression of virulence factors could not be established, targeted transcriptional analysis indicates that a possible association between (p)ppGpp and c-di-AMP signaling pathways in response to the conditions found in the bladder may play a role in enterococcal CAUTI. Collectively, data from this study identify the (p)ppGpp-CodY network as an important contributor to enterococcal virulence in catheterized mouse bladder and support that basal (p)ppGpp pools and CodY promote virulence through maintenance of a balanced metabolism under adverse conditions.IMPORTANCE Catheter-associated urinary tract infections (CAUTIs) are one of the most frequent types of infection found in the hospital setting that can develop into serious and potentially fatal bloodstream infections. One of the infectious agents that frequently causes complicated CAUTI is the bacterium Enterococcus faecalis, a leading cause of hospital-acquired infections that are often difficult to treat due to the exceptional multidrug resistance of some isolates. Understanding the mechanisms by which E. faecalis causes CAUTI will aid in the discovery of new druggable targets to treat these infections. In this study, we report the importance of two nutrient-sensing bacterial regulators, named (p)ppGpp and CodY, for the ability of E. faecalis to infect the catheterized bladder of mice.

Necrotizing fasciitis after spinal anesthesia.

Regional anesthesia is the preferred technique for Cesarean delivery. Strict aseptic precautions should be taken; otherwise, infectious complications including abscess formation, meningitis and necrotizing fasciitis may result. We report a case of a 26-year-old post-partum female who presented with necrosis of the skin of back following spinal anesthesia, which was administered for Cesarean delivery 5 days prior at a private nursing home. On presentation, she was drowsy, appeared dehydrated and febrile. Examination of her back revealed necrosis of skin extending from just below the scapula to the gluteal region. Debridement of skin over the back was performed, and intravenous antibiotics started. After three debridements following which skin grafting was performed, she made complete recovery. Infectious complications following regional anesthesia are rare, and most of the literature focuses on colonization of epidural catheters or epidural abscess. There is no report of necrotizing fasciitis following spinal anesthesia so far. Sources of infection that are suspected in our case include: local anesthetic solution used for subcutaneous infiltration, nonadherence to aseptic precautions, skin flora of patient, endogenous source and nasopharyngeal flora of anesthesiologist. We considered each possibility, and the most likely cause in our case appears to be infection from an already-used vial of a local anesthetic agent. Local anesthetics have bacteriostatic properties, but infection may still be transmitted through contaminated solutions. The present case highlights the importance of maintaining strict aseptic precautions, avoiding reusing multidose vials and early recognition of this complication as timely intervention can be lifesaving.

Uniocular ptosis due to cysticercosis of extraocular muscle.

Involvement of extraocular muscle by Cysticercus cellulosae is very rare. Rarer still is the isolated involvement of the levator palpebrae superioris muscle presenting clinically as ptosis. We report here such a presentation in an eleven years old girl.

Damage to the anterior visual pathway and brain parenchyma following external pituitary irradiation.

Three cases of damage to the optic nerves and chiasma following pituitary irradiation with Co60 teletherapy are described. All of them presented with progressive visual impairment months following irradiation and simulated recurrence of the tumour. CT scan was also not helpful in differentiating radionecrosis from tumour recurrence. On exploration the optic nerves and chiasma appeared discoloured and scarred. One case, who also had diffuse radionecrosis of brain parenchyma, died. No satisfactory therapy is currently available for this grave complication but proper safeguards can prevent it.