Analysis of the Destabilization of Bacterial Membranes by Quaternary Ammonium Compounds: A Combined Experimental and Computational Study.

The mechanism of action of quaternary ammonium compound (QAC) antiseptics has long been assumed to be straightforward membrane disruption, although the process of approaching and entering the membrane has little modeling precedent. Furthermore, questions have more recently arisen regarding bacterial resistance mechanisms, and why select classes of QACs (specifically, multicationic QACs) are less prone to resistance. In order to better understand such subtleties, a series of molecular dynamics simulations were utilized to help identify these molecular determinants, directly comparing mono-, bis-, and triscationic QACs in simulated membrane intercalation models. Three distinct membranes were simulated, mimicking the surfaces of Escherichia coli and Staphylococcus aureus, as well as a neutral phospholipid control. By analyzing the resulting trajectories in the form of a timeseries analysis, insight was gleaned regarding the significant steps and interactions involved in the destabilization of phospholipid bilayers within the bacterial membranes. Finally, to more specifically probe the effect of the hydrophobic section of the amphiphile that presumably penetrates the membrane, a series of alkyl- and ester-based biscationic quaternary ammonium compounds were prepared, tested for antimicrobial activity against both Gram-positive and Gram-negative bacteria, and modeled.

Descriptive Patterns of Deafness Among Pre-School Saudi Children Aged Two to Five Years Visiting Neurology Clinic From 2012 to 2017.

Background Early childhood years are very important and crucial periods for developing different developmental milestones. Hearing loss is considered to be one of the most commonly detectable problems, which often goes unnoticed or not given proper attention due to the lack of screening modalities or the inability of parents or guardians to recognize it in early stages. Therefore, it is necessary to determine the pattern of differences pertaining to hearing loss among pre-school children of various age groups to better approach this issue in a systemic and fundamental manner, so that better care and treatment can be provided to children suffering from deafness. Methods This study involved a descriptive, retrospective chart review in two hospital settings, and it was conducted at the department of physiology (neurophysiology) of King Abdulaziz and King Khalid University Hospitals at the King Saud University (KSU) in Riyadh during the period of 2012-2017. A total of 324 pre-school Saudi children from the age of two to five years were involved and tested by brainstem auditory evoked potentials (BAEPs) to assess deafness. Results A total of 324 patients underwent the BAEP test; of them, 199 (61.4%) were males and 125 (38.6%) were females. Regarding the age groups, the most common age group was that of two-year-olds with 117 (36.1%) participants, followed by three-year-olds with 80 (24.7%) children, four-year-olds with 73 (22.5%) patients, and five-year-olds with 54 (16.7%) participants. Furthermore, there were 220 (67.9%) patients with sensorineural hearing loss (SNHL), 92 (28.4%) with conductive hearing loss (CHL), four (1.2%) with mixed hearing loss (MHL), and eight (2.5%) with normal audiometry. The normal hearing threshold was determined to be 20 dB, and the mean value for the hearing threshold of the SNHL in the right ear was found to be 43.45 ± 25.85, while the left-ear mean value was 44.54 ± 28.78. The mean value of the hearing threshold in CHL of the right ear was 50.96 ± 22.23, while that of the left ear was 47.85 ± 22.74. Lastly, the mean value of the hearing threshold in MHL of the right ear was 80.00 ± 21.21, while that of the left ear was 73.75 ± 18.87. Conclusion SNHL was the most common type (67.9%) of pre-school hearing loss in Saudi Children attending the neurophysiology clinic at KSU hospitals between 2012-2017, while MHL constituted the most severe cases.

Changes in Microbiome Confer Multigenerational Host Resistance after Sub-toxic Pesticide Exposure.

The gut is a first point of contact with ingested xenobiotics, where chemicals are metabolized directly by the host or microbiota. Atrazine is a widely used pesticide, but the role of the microbiome metabolism of this xenobiotic and the impact on host responses is unclear. We exposed successive generations of the wasp Nasonia vitripennis to subtoxic levels of atrazine and observed changes in the structure and function of the gut microbiome that conveyed atrazine resistance. This microbiome-mediated resistance was maternally inherited and increased over successive generations, while also heightening the rate of host genome selection. The rare gut bacteria Serratia marcescens and Pseudomonas protegens contributed to atrazine metabolism. Both of these bacteria contain genes that are linked to atrazine degradation and were sufficient to confer resistance in experimental wasp populations. Thus, pesticide exposure causes functional, inherited changes in the microbiome that should be considered when assessing xenobiotic exposure and as potential countermeasures to toxicity.