Acute primary angle closure during the Omicron outbreak.

AIM: To investigate Omicron's impact on clinical presentation of acute primary angle closure (APAC) in China. METHODS: A consecutive case series with historical controls was conducted at Shenzhen Eye Hospital, the largest specialized hospital in Shenzhen, China. Medical records from a two-month period during the Omicron pandemic (December 1, 2022, to January 31, 2023) were compared with records from two control groups (12/2018-1/2019 and 12/2021-1/2022) before pandemic. Patients with APAC were included, and the prevalence of APAC and demographic characteristics in Omicron-infected and non-infected patients were compared. RESULTS: Seventy-one (23.43%) out of 303 patients were diagnosed with APAC in the pandemic cohort, which was 2.98 and 2.61 times higher than that in control cohorts (7.87% in 2019, 8.96% in 2022, P<0.001). The pandemic cohort has significantly higher Omicron-infected rate (78.87% vs 0 vs 0; P<0.001), lower proportion of glaucoma history (16.90% vs 42.86% vs 41.67%, P=0.005), higher surgical rate (95.77% vs 83.33% vs 78.57%, P=0.024), higher total medical costs and larger pupil diameter (5.63±0.15 vs 4.68±0.15 vs 4.69±0.22 mm, P<0.01). In 83% Omicron-infected patients, ocular symptoms appeared within 3d after systemic symptoms onset. In multivariate analysis, Omicron infection (P<0.001) was the only independent predictor of pupil diameter. CONCLUSION: In the Omicron epidemic in China, there is an increase of prevalence and severity of APAC, particularly focusing on the first 3d following infection.

Novel Quantitative Contrast Sensitivity Function Enhances the Prediction of Treatment Outcome and Recurrence in Amblyopia.

Purpose: Although effective amblyopia treatments are available, treatment outcome is unpredictable, and the condition recurs in up to 25% of the patients. We aimed to evaluate whether a large-scale quantitative contrast sensitivity function (CSF) data source, coupled with machine learning (ML) algorithms, can predict amblyopia treatment response and recurrence in individuals. Methods: Visual function measures from traditional chart vision acuity (VA) and novel CSF assessments were used as the main predictive variables in the models. Information from 58 potential predictors was extracted to predict treatment response and recurrence. Six ML methods were applied to construct models. The SHapley Additive exPlanations was used to explain the predictions. Results: A total of 2559 consecutive records of 643 patients with amblyopia were eligible for modeling. Combining variables from VA and CSF assessments gave the highest accuracy for treatment response prediction, with the area under the receiver operating characteristic curve (AUC) of 0.863 and 0.815 for outcome predictions after 3 and 6 months, respectively. Variables from the VA assessment alone predicted the treatment response, with AUC values of 0.723 and 0.675 after 3 and 6 months, respectively. Variables from the CSF assessment gave rise to an AUC of 0.909 for recurrence prediction compared to 0.539 for VA assessment alone, and adding VA variables did not improve predictive performance. The interocular differences in CSF features are significant contributors to recurrence risk. Conclusions: Our models showed CSF data could enhance treatment response prediction and accurately predict amblyopia recurrence, which has the potential to guide amblyopia management by enabling patient-tailored decision making.

Binocular Summation With Quantitative Contrast Sensitivity Function: A Novel Parameter to Evaluate Binocular Function in Intermittent Exotropia.

Purpose: Intermittent exotropia (IXT) is the most common form of strabismus. Surgery can potentially improve binocular function in patients with IXT. We aimed to evaluate binocular function using a novel parameter-binocular summation ratio (BSR), measured using quantitative contrast sensitivity function (CSF) in patients with IXT before and after surgery. Methods: Prospective study of 63 patients with IXT and 41 healthy controls were consecutively enrolled and underwent quantitative CSF testing binocularly and monocularly. BSR was calculated by dividing the CSF of the binocular value by the better monocular value. Forty-eight patients with IXT underwent strabismus surgery. BSR, stereoacuity, fusion ability, and strabismus questionnaires were assessed pre-operatively and 2 months postoperatively. Results: Sixty-three patients with IXT (median age = 9 years) compared with 41 healthy controls showed a worse mean BSR based on all CSF metrics at baseline (the area under the log CSF [AULCSF], spatial frequency [SF] cutoff, and contrast sensitivity at 1.0-18.0 cpd SF). All 48 patients with IXT showed successful alignment after surgery, and there were significant improvements in BSR based on the AULCSF, SF cutoff, and contrast sensitivity at 6.0, 12.0, and 18.0 cpd SF, respectively. The distance stereoacuity and fusion ability also improved after surgery, and a better BSR was associated with better stereoacuity and fusion. For strabismus questionnaires, the psychosocial subscale scores improved postoperatively, whereas the functional subscale scores did not change. Conclusions: BSR based on quantitative CSF can characterize binocular function across a range of spatial frequencies and can be used as a supplemental measurement for monitoring binocularity in patients with IXT in clinical settings.

Perceptual Learning Based on the Lateral Masking Paradigm in Anisometropic Amblyopia With or Without a Patching History.

Purpose: Perceptual learning (PL) has shown promising performance in restoring visual function in adolescent amblyopes. We retrospectively compared the effect of a well-accepted PL paradigm on patients with anisometropic amblyopia with or without a patching therapy history (patching therapy [PT] group versus no patching therapy [NPT] group). Methods: Eighteen PT and 13 NPT patients with anisometropic amblyopia underwent monocular PL for 3 months. During training, patients practiced a Gabor detection task following the lateral masking paradigm by applying a temporal two-alternative forced choice procedure with the amblyopic eye. Monocular contrast sensitivity functions (CSF), visual acuity, interocular differences in visual function metrics, and stereoacuity were compared before and after training. Results: PL improved the visual acuity of the amblyopia eyes by 0.5 lines on average in the PT group and 1.5 lines in the NPT group. A significant reduction in the interocular difference in visual acuity was observed in the NPT group (P < 0.01) but not in the PT group (P = 0.05). Regarding CSF metrics, the area under the log CSF and cutoff in the amblyopic eyes of the NPT groups increased after training (P < 0.05). In addition, the interocular differences of the CSF metrics (P < 0.05) in the NPT group were significantly reduced. However, in the PT group, all the CSF metrics were unchanged after training. A total of 27 of 31 patients in both groups had no measurable stereopsis pretraining, and recovery after training was not significant. Conclusions: PL based on a lateral masking training paradigm improved visual function in anisometropic amblyopia. Patients without a patching history achieved greater benefits. Translational Relevance: PL based on a lateral masking training paradigm could be a new treatment for amblyopia.

Hyperoside alleviates photoreceptor degeneration by preventing cell senescence through AMPK-ULK1 signaling.

Vision loss and blindness are frequently caused by photoreceptor degeneration, for example in age-related macular degeneration and retinitis pigmentosa. However, there is no effective medicine to treat these photoreceptor degeneration-related diseases. Cell senescence is a common phenotype in many diseases; however, few studies have reported whether it occurs in photoreceptor degeneration diseases. Herein, we identified that cell senescence is associated with photoreceptor degeneration induced by N-methyl-N-nitrosourea (MNU, a commonly used photoreceptor degeneration model), presented as increased senescence-associated ß-galactosidase activity, DNA damage, oxidative stress and inflammation-related cytokine Interleukin 6 (IL6), and upregulation of cyclin p21 or p16. These results suggested that visual function might be protected using anti-aging treatment. Furthermore, Hyperoside is reported to help prevent aging in various organs. In this study, we showed that Hyperoside, delivered intravitreally, alleviated photoreceptor cell senescence and ameliorated the functional and morphological degeneration of the retina in vivo and in vitro. Importantly, Hyperoside attenuated the MNU-induced injury and aging of photoreceptors via AMPK-ULK1 signaling inhibition. Taken together, our results demonstrated that Hyperoside can prevent MNU-induced photoreceptor degeneration by inhibiting cell senescence via the AMPK-ULK1 pathway.

Analysis of shared ceRNA networks and related-hub genes in rats with primary and secondary photoreceptor degeneration.

Introduction: Photoreceptor degenerative diseases are characterized by the progressive death of photoreceptor cells, resulting in irreversible visual impairment. However, the role of competing endogenous RNA (ceRNA) in photoreceptor degeneration is unclear. We aimed to explore the shared ceRNA regulation network and potential molecular mechanisms between primary and secondary photoreceptor degenerations. Methods: We established animal models for both types of photoreceptor degenerations and conducted retina RNA sequencing to identify shared differentially expressed long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs). Using ceRNA regulatory principles, we constructed a shared ceRNA network and performed function enrichment and protein-protein interaction (PPI) analyses to identify hub genes and key pathways. Immune cell infiltration and drug-gene interaction analyses were conducted, and hub gene expression was validated by quantitative real-time polymerase chain reaction (qRT-PCR). Results: We identified 37 shared differentially expressed lncRNAs, 34 miRNAs, and 247 mRNAs and constructed a ceRNA network consisting of 3 lncRNAs, 5 miRNAs, and 109 mRNAs. Furthermore, we examined 109 common differentially expressed genes (DEGs) through functional annotation, PPI analysis, and regulatory network analysis. We discovered that these diseases shared the complement and coagulation cascades pathway. Eight hub genes were identified and enriched in the immune system process. Immune infiltration analysis revealed increased T cells and decreased B cells in both photoreceptor degenerations. The expression of hub genes was closely associated with the quantities of immune cell types. Additionally, we identified 7 immune therapeutical drugs that target the hub genes. Discussion: Our findings provide new insights and directions for understanding the common mechanisms underlying the development of photoreceptor degeneration. The hub genes and related ceRNA networks we identified may offer new perspectives for elucidating the mechanisms and hold promise for the development of innovative treatment strategies.

Impact of COVID-19 pandemic control measures on amblyopia treatment: a retrospective study of records from a tertiary eye hospital in China.

OBJECTIVES: Amblyopia is the most common cause of unilateral visual impairment in children and requires long-term treatment. This study aimed to quantify the impact of pandemic control measures on amblyopia management. DESIGN AND SETTING: This was a retrospective cohort study of data from a large amblyopia management database at a major tertiary eye care centre in China. PARTICIPANTS: Outpatients with amblyopia who visited the hospital from 1 June 2019, through 28 February 2022. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the number of first and follow-up in-person visits to the hospital for amblyopia treatment. Secondary outcomes included the time interval between consecutive visits and improvement of vision (visual acuity, contrast sensitivity and stereopsis). Patient records were grouped into prepandemic and during pandemic periods. RESULTS: A total of 10 060 face-to-face visits for 5361 patients (median age 6.7 years, IQR 5.4, 8.9) that spanned two lockdown periods were included in the analysis, of which 28% were follow-up visits. Pandemic control measures caused a sharp decline in the number of outpatient visits (3% and 30% of prepandemic levels in the months directly after the start of the first (2020) and second (2021) periods of pandemic control measures, respectively). However, these drops were followed by pronounced rebounds in visits that exceeded prepandemic levels by 51.1% and 108.5%, respectively. The interval between consecutive visits increased significantly during the pandemic from a median (IQR) of 120 (112, 127) days in 2019 to 197 (179, 224) in 2020 (p<0.001) and 189 (182, 221) in 2021 (p<0.001). There were no significant differences in the improvement of visual function or treatment compliance between the prepandemic and postpandemic groups. CONCLUSIONS: The number of amblyopia patient hospital visits spiked well above prepandemic levels following lockdown periods. This pattern of patient behaviour can inform planning for amblyopia treatment services during and after public health-related disruptions.

Characteristics and predictive factors of visual function improvements after monocular perceptual learning in amblyopia.

Monocular perceptual learning has shown promising performance in restoring visual function in amblyopes beyond the critical period in the laboratory. However, the treatment outcome is variable and indeterminate in actual clinical and neuroscientific practice. We aimed to explore the efficacy of monocular perceptual learning in the clinical setting. By combining continuous monitoring of perceptual learning and clinical measurements, we evaluated the efficacy and characteristics of visual acuity and contrast sensitivity function improvement and further explored the individualized effect after perceptual learning. Amblyopes (average age:17 ± 7 years old) were trained in a monocular two-alternative forced choice identification task at the 50% contrast threshold of the amblyopic eye for 10-15 days. We found that monocular perceptual learning improves both visual acuity and contrast sensitivity function in amblyopia. The broader activation of spatial contrast sensitivity, with a significant improvement in lower spatial frequencies, contributed to improving visual acuity. Visual acuity changes in the early stage can predict the endpoint treatment outcomes. Our results confirm the efficacy of monocular perceptual learning and suggest potential predictors of training outcomes to assist in the future management of clinical intervention and vision neuroscience research in amblyopia beyond the critical period of visual plasticity.

Factors predicting regression of visual acuity following successful treatment of anisometropic amblyopia.

Objective: To identify factors associated with visual acuity regression following successful treatment of anisometropic amblyopia. Design and method: This was a retrospective cohort study. Database records for 100 and 61 children with anisometropic amblyopia who met at least one criterion for successful treatment proposed by the Pediatric Eye Disease Investigator Group (PEDIG) and had at least 1 year of follow-up data available after the criterion was met were analyzed. The study sample was split into two groups, those who regressed within 1 year of successful treatment (no longer met any of the PEDIG criteria for successful treatment) and those who did not. A two-step analysis involving a least absolute shrinkage and selection operator (LASSO) regression and a logistic regression were used to identify predictor variables for increased risk of regression. A broad range of clinical, perceptual, and demographic variables were included in the analyses. Results: Sixty-eight (42.5%) children regressed within 1 year of successful treatment. Among the 27 predictor variables considered within the statistical modeling process, the three most important for predicting treatment regression were the extent of amblyopic eye visual acuity improvement, age at first hospital visit and sex. Specifically, lower risk of regression was associated with larger amblyopic eye visual acuity improvement with treatment, younger age at initiation of treatment and female sex. Conclusion: Patients who received treatment at a younger age and responded well to treatment had a lower risk of treatment regression. This pattern of results suggests that early detection of amblyopia and strategies that enhance treatment adherence may reduce the risk of treatment regression. The higher risk of regression in boys than girls that we observed may reflect known sex differences in brain development and /or sex differences in environment within our sample of children from South China.

Assessing the contrast sensitivity function in myopic parafovea: A quick contrast sensitivity functions study.

Purpose: Compare peripheral contrast sensitivity functions (CSF) between myopes and emmetropes to reveal potential myogenic risks during emmetropization. Materials and methods: This observational, cross-sectional, non-consecutive case study included data from 19 myopes (23.42 ± 4.03 years old) and 12 emmetropes (22.93 ± 2.91 years old) who underwent central and peripheral quick CSF (qCSF) measurements. Summary CSF metrics including the cut-off spatial frequency (cut-off SF), area under log CSF (AULCSF), low-, intermediate-, and high-spatial-frequency AULCSFs (l-, i-, and h-SF AULCSFs), and log CS at 19 SFs in the fovea and 15 peripheral locations (superior, inferior, temporal, and nasal quadrants at 6, 12, 18, and 24° eccentricities, excluding the physiological scotoma at 18°) were analyzed with 3-way and 4-way between-subjects analysis of variance (ANOVA) (α = 0.05). Results: Three-way ANOVA showed that myopes had significantly increased AULCSF at 6° (mean difference, 0.08; 95% CI, 0.02-0.13; P = 0.007) and 12° (mean difference, 0.09; 95% CI, 0.03-0.14; P = 0.003). Log CS at all 19 SFs were higher in the myopia group compared to the normal group (mean differencesuperior, 0.02; 95% CI, 0.01-0.20; P = 0.02 and mean differenceinferior, 0.11; 95% CI, 0.02-0.21; P = 0.01) at 12°. The h-SF AULCSF at 6° (mean differenceinferior, 1.27; 95% CI, 0.32-2.22; P = 0.009) and i-SF AULCSF at 12° (mean differencesuperior, 5.31; 95% CI, 4.35-6.27; P < 0.001; mean differenceinferior, 1.14; 95% CI, 0.19-2.10; P = 0.02) were higher in myopia vs. normal group. Conclusion: We found myopia increased contrast sensitivity in superior and inferior visual field locations at 6° parafoveal and 12° perifoveal regions of the retina. The observation of increased contrast sensitivities within the macula visual field in myopia might provide important insights for myopia control during emmetropization.

Contrast Sensitivity and Stereoacuity in Successfully Treated Refractive Amblyopia.

Purpose: To assess whether monocular contrast sensitivity and stereoacuity impairments remain when visual acuity is fully recovered in children with refractive amblyopia. Methods: A retrospective review of 487 patients diagnosed with refractive amblyopia whose visual acuity improved to 0.08 logMAR or better in both eyes following optical treatment was conducted. Measurements of monocular contrast sensitivity and stereoacuity had been made when visual acuity normalized. All patients had been treated with refractive correction for approximately 2 years following diagnosis. No other treatments were provided. Monocular contrast sensitivity was measured using the CSV-1000E chart for children 6 years of age or younger and a psychophysical technique called the quick contrast sensitivity function in older children. Stereoacuity was measured using the Random Dot Test that includes monocular cues and the Randot Stereoacuity Test that does not have monocular cues. Results: Statistically significant interocular differences in contrast sensitivity were observed. These differences tended to occur at higher spatial frequencies (12 and 18 cycles per degree). Stereoacuity within the age-specific normal range was achieved by 47.4% of patients for the Random Dot Test and only 23.1% of patients for the Randot Stereoacuity Test. Conclusions: Full recovery of visual acuity following treatment for refractive amblyopia does not equalize interocular contrast sensitivity or restore normal stereopsis. Alternative therapeutic approaches that target contrast sensitivity and/or binocular vision are required.

The Integration of Eye Tracking Responses for the Measurement of Contrast Sensitivity: A Proof of Concept Study.

Contrast sensitivity (CS) is important when assessing functional vision. However, current techniques for assessing CS are not suitable for young children or non-verbal individuals because they require reliable, subjective perceptual reports. This study explored the feasibility of applying eye tracking technology to quantify CS as a first step toward developing a testing paradigm that will not rely on observers' behavioral or language abilities. Using a within-subject design, 27 healthy young adults completed CS measures for three spatial frequencies with best-corrected vision and lens-induced optical blur. Monocular CS was estimated using a five-alternative, forced-choice grating detection task. Thresholds were measured using eye movement responses and conventional key-press responses. CS measured using eye movements compared well with results obtained using key-press responses [Pearson's r best-corrected = 0.966, P < 0.001]. Good test-retest variability was evident for the eye-movement-based measures (Pearson's r = 0.916, P < 0.001) with a coefficient of repeatability of 0.377 log CS across different days. This study provides a proof of concept that eye tracking can be used to automatically record eye gaze positions and accurately quantify human spatial vision. Future work will update this paradigm by incorporating the preferential looking technique into the eye tracking methods, optimizing the CS sampling algorithm and adapting the methodology to broaden its use on infants and non-verbal individuals.

Sensitivity and Stability of Functional Vision Tests in Detecting Subtle Changes Under Multiple Simulated Conditions.

Purpose: To explore whether subtle changes in visual quality can be detected using different measures of visual function against the quick contrast sensitivity function test (quick CSF). Methods: Sixty participants, aged 17 to 34 years, were enrolled. Participants' vision was degraded by 0.25 D undercorrection (0.25 D), 60% neutral density filter brightness reduction (60% ND), and 0.8 Bangerter foil optical diffusion (0.8BAN). Visual function tests including visual acuity and contrast sensitivity (CSV-1000E and quick CSF) were measured with participant's best-corrected vision and under simulated visual degradation conditions. Test sensitivities in detecting differences were compared. Results: Statistically significant visual acuity degradation was observed in the 0.8BAN condition only (Pcorrected < 0.001). With CSV-1000E and outliers removed, significant CS degradation was observed in all spatial frequencies, area under log CSF (AULCSF) in the 0.8BAN condition (Pcorrected < 0.001 for all), medium and high spatial frequencies and AULCSF in the 60%ND condition (Pcorrected,6cpd = 0.002, Pcorrected,12cpd = 0.005, Pcorrected,18cpd = 0.001, Pcorrected,AULCSF < 0.001) and the 0.25 D condition (Pcorrected,6cpd = 0.011, Pcorrected,12cpd = 0.013, Pcorrected,18cpd = 0.015, Pcorrected,AULCSF < 0.001). With the quick CSF, significant CS degradation was observed in all simulated visual conditions in all spatial frequencies, cutoff frequency and AULCSF (Pcorrected < 0.001 for all). Test-retest reliability of the quick CSF method was high; coefficient of repeatability ranged from 0.14 to 0.18 logCS. Conclusions: Compared with visual acuity and chart-based CS tests, the quick CSF method provided more reliable and sensitive measures to detect small visual changes. Translational Relevance: The quick CSF method can provide sensitive and reliable measures to monitor disease progression and assess treatment outcomes.

Meridian-Specific and Post-Optical Deficits of Spatial Vision in Human Astigmatism: Evidences From Psycho-Physical and EEG Scalings.

Previous studies have demonstrated that orientation-specific deprivation in early life can lead to neural deficits of spatial vision in certain space, and can even result in meridional amblyopia (MA). Individuals with astigmatism are the optimal and natural models for exploring this asymmetric development of spatial vision in the human visual system. This study aims to assess the contrast sensitivity function (CSF) and EEG signals along two principal meridians in participants with regular astigmatism when being optimal optical corrected. Twelve participants with astigmatism (AST group, 20 eyes) and thirteen participants with (MA group, 19 eyes) were recruited in the current study. CSFs and spatial sweep visual evoked potentials (sVEP) were measured with vertical and horizontal sinewave gratings along two principal meridians monocularly. Area under log CSF (AULCSF), spatial frequency threshold corresponding to 80% contrast gratings (SF threshold at 80% ctr), and CSF acuity were calculated from CSF test. In addition, sVEP amplitudes and thresholds were calculated with the recursive least square method. Participants with astigmatism exhibited marked vertical-horizontal resolution disparities even after they were corrected with optimal optical corrections. CSF tests showed that AULCSF along weak meridian (measured with horizontal gratings) was lower than that along strong meridian (measured with vertical gratings) in both groups. Significant meridional disparity of CSF acuity was also found in both groups. In addition, the MA group showed larger meridional disparity compared to the AST group. Spatial sVEP thresholds also supported the existence of marked meridional disparity. Our results suggest that meridian-specific partial deprivation in early life might lead to monocularly asymmetric development of spatial vision in the human visual system. In terms of application, we tested the feasibility and reliability of adopting psychophysical and EEG scalings to investigate the asymmetric development of spatial vision related to astigmatism. These paradigms are potentially applicable to reduce and even eliminate the meridional disparity in the primary visual cortex by adopting perceptual learning or other vision-related interventions.

Co-existence of Citrobacter freundii exacerbated Pseudomonas aeruginosa infection in vivo.

The presence of bacterial species other than the pathogen at infection site can affect the progression of a bacterial infection. Based on the fact that Citrobacter freundii can coexist during Pseudomonas aeruginosa infection, this study aims to investigate the impact of the co-existing C. freundii on the pathogenesis of P. aeruginosa infection. A murine peritonitis model was used to compare the mortality rates and histopathology of P. aeruginosaPAO1 infection in the presence and absence of a C. freundii clinical isolate C9. We also investigated the intercellular interaction between PAO1 and C9 by examining pyocyanin production and comparing gene expression levels. The results demonstrate that co-infection with C9 significantly increased the mortality rate and tissue damages in PAO1 infected mice. At an inoculum of 106 CFU, no mortality was observed in the C9 infected group at three days post-infection, whereas the mortality rate in the PAO1-C9 co-infection group was 64%, compared with 24% in the PAO1 infected group. Pyocyanin production in P. aeruginosa PAO1 increased 8 folds approximately in the presence of C. freundii C9, and operons associated with phenazine synthesis, phzA1 and phzA2, were also upregulated. Disruption of the phzA1 and phzA2 eliminated the exacerbated pathogenicity in the co-infection group, indicating that the elevated pyocyanin production was the main contributing factor. The results suggest that co-existing C. freundii during P. aeruginosa infection can exacerbate the pathogenicity, which may have significant implications in patients infected with these bacteria.

YhjX Regulates the Growth of Escherichia coli in the Presence of a Subinhibitory Concentration of Gentamicin and Mediates the Adaptive Resistance to Gentamicin.

The mechanisms of adaptive resistance of Escherichia coli to aminoglycosides remain unclear. Our RNA-Seq study found that expression of yhjX was markedly upregulated during initial exposure to subinhibitory concentrations of gentamicin. The expression of yhjX was then downregulated dramatically during a second exposure to gentamicin compared to the first exposure. YhjX encodes a putative transporter of the major facilitator superfamily, which is known to be the sole target of the YpdA/YpdB two-component system, the expression of which is highly and specifically induced by pyruvate. To investigate the effect of yhjX on the adaptive resistance of E. coli, in the present study, we constructed yhjX deletion and complemented strains of E. coli ATCC25922. Changes in extracellular pyruvate levels of wide-type and yhjX mutant were measured to determine whether YhjX functions as a pyruvate transporter. The results showed that yhjX deletion improved the growth of E. coli in medium containing subinhibitory concentrations of gentamicin. The yhjX deletion mutant did not exhibit adaptive resistance to subinhibitory concentrations of gentamicin. YhjX might not function as a pyruvate efflux pump in E. coli but was associated with the decrease following a sharp increase in the extracellular pyruvate level. Our findings indicate that yhjX regulates the growth of E. coli in the presence of a subinhibitory concentration of gentamicin and mediates the adaptive resistance to gentamicin.

Short-Term Pretreatment of Sub-Inhibitory Concentrations of Gentamycin Inhibits the Swarming Motility of Escherichia Coli by Down-Regulating the Succinate Dehydrogenase Gene.

BACKGROUND/AIMS: Motility is a feature of many pathogens that contributes to the migration and dispersion of the infectious agent. Whether gentamycin has a post-antibiotic effect (PAE) on the swarming and swimming motility of Escherichia coli (E. coli) remains unknown. In this study, we aimed to examine whether short-term pretreatment of sub-inhibitory concentrations of gentamycin alter motility of E. coli and the mechanisms involved therein. METHODS: After exposure to sub-inhibitory concentrations (0.8 µg/ml) of gentamicin, the swarming and swimming motility of E. coli was tested in semi-solid media. Real-time PCR was used to detect the gene expression of succinate dehydrogenase (SDH). The production of SDH and fumarate by E. coli pretreated with or without gentamycin was measured. Fumarate was added to swarming agar to determine whether fumarate could restore the swarming motility of E. coli. RESULTS: After pretreatment of E. coli with sub-inhibitory concentrations of gentamycin, swarming motility was repressed in the absence of growth inhibition. The expression of all four subunits of SDH was down-regulated, and the intracellular concentration of SDH and fumarate, produced by E. coli, were both decreased. Supplementary fumarate could restore the swarming motility inhibited by gentamycin. A selective inhibitor of SDH (propanedioic acid) could strongly repress the swarming motility. CONCLUSION: Sub-inhibitory concentrations of gentamycin inhibits the swarming motility of E. coli. This effect is mediated by a reduction in cellular fumarate caused by down-regulation of SDH. Gentamycin may be advantageous for treatment of E. coli infections.