Measuring Spatial Access of Vulnerable Population to HIV Testing Facilities in the Baton Rouge Metropolitan Statistical Area, Louisiana.

Ensuring adequate and equitable access to affordable HIV testing is a crucial step toward ending the HIV epidemic (EHE). Using the high-burden Baton Rouge Metropolitan Statistical Area (MSA) as an example, we measure spatial access to HIV testing facilities for vulnerable populations and assess whether their access would improve if eliminating a considerable barrier-costs. Locations and status (free, low-cost, and full cost) of HIV testing facilities are searched on the Internet and confirmed through a field survey. Vulnerable populations include the uninsured and people living with HIV (PLWH), disaggregated from county-level HIV prevalence data. Spatial access is computed by a normalized urban-rural two-step floating catchment area (NUR2SFCA) method. Our survey confirms that only 11% and 37% of the 103 Internet-searched HIV testing facilities are indeed free and low-cost. Making more facilities cheaper or free increases the average access of PLWH, the uninsured, and the entire population but their geographic patterns vary. Free testing facilities, clustered in Baton Rouge city, are highly accessible to 82.6%, 69.4%, and 70.2% of three population groups living in East and West Baton Rouge Parish. In comparison, making all low-cost facilities free increases access in most outlying parishes but at the cost of reducing access in East Baton Rouge Parish, leaving west Livingston, north Iberville, and east Pointe Coupee Parish with the poorest access. Making all full-cost facilities cheaper or free exhibits a similar pattern. The study has important policy implications for where and how to improve access to HIV testing for vulnerable populations.

RESUMEN: Medimos el acceso espacial a las instalaciones de pruebas de VIH para poblaciones vulnerables y evaluamos si su acceso mejoraría si se eliminaran las barreras de costos, utilizando como ejemplo el área estadística metropolitana de Baton Rouge, que tiene una alta carga. Nuestra encuesta confirma que el 11% y el 37% de los 103 centros de pruebas de VIH buscados en Internet son efectivamente gratuitos y de bajo costo. Hacer que más instalaciones sean más baratas o gratuitas aumenta el acceso promedio de las PLWH, las personas sin seguro y toda la población, pero sus patrones geográficos varían. Las instalaciones de pruebas gratuitas, agrupadas en la ciudad de Baton Rouge, son muy accesibles para el 82,6%, el 69,4% y el 70,2% de los tres grupos de población del este y oeste de Baton Rouge. En comparación, hacer que las instalaciones de bajo costo sean gratuitas aumenta el acceso en las parroquias periféricas, pero a costa de reducir el acceso en East Baton Rouge. Hacer que las instalaciones de costo total sean más baratas o gratuitas muestra un patrón similar. El estudio tiene importantes implicaciones políticas para mejorar el acceso a las pruebas del VIH para las poblaciones vulnerables.

Rural-Urban Differences in Breast Cancer Surgical Delays in Medicare Beneficiaries.

BACKGROUND: Delays between breast cancer diagnosis and surgery are associated with worsened survival. Delays are more common in urban-residing patients, although factors specific to surgical delays among rural and urban patients are not well understood. METHODS: We used a 100% sample of fee-for-service Medicare claims during 2007-2014 to identify 238,491 women diagnosed with early-stage breast cancer undergoing initial surgery and assessed whether they experienced biopsy-to-surgery intervals > 90 days. We employed multilevel regression to identify associations between delays and patient, regional, and surgeon characteristics, both in combined analyses and stratified by rurality of patient residence. RESULTS: Delays were more prevalent among urban patients (2.5%) than rural patients (1.9%). Rural patients with medium- or high-volume surgeons had lower odds of delay than patients with low-volume surgeons (odds ratio [OR] = 0.71, 95% confidence interval [CI] = 0.58-0.88; OR = 0.74, 95% CI = 0.61-0.90). Rural patients whose surgeon operated at ≥ 3 hospitals were more likely to experience delays (OR = 1.29, 95% CI = 1.01-1.64, Ref: 1 hospital). Patient driving times ≥ 1 h were associated with delays among urban patients only. Age, black race, Hispanic ethnicity, multimorbidity, and academic/specialty hospital status were associated with delays. CONCLUSIONS: Sociodemographic, geographic, surgeon, and facility factors have distinct associations with > 90-day delays to initial breast cancer surgery. Interventions to improve timeliness of breast cancer surgery may have disparate impacts on vulnerable populations by rural-urban status.

Effects of Long-Term and Multigeneration Exposure of Caenorhabditis elegans to 9.4 GHz Microwaves.

A large number of studies on the biological effects of microwaves are carried out using rodents and cells, but the conditions are difficult to control, and the irradiation period is short; the results obtained have always been controversial and difficult to reproduce. In this study, we expose nematodes to an electromagnetic environment for a long-term and multigeneration period to explore the possible biological effects. Wild-type N2 strains of Caenorhabditis elegans are exposed to 9.4 GHz microwaves at a specific adsorption rate of 4 W/kg for 10 h per day from L1 larvae to adults. Then, adult worms are washed off, and the laid eggs are kept to hatch L1 larvae, which are continuously exposed to microwaves until passing through 20 generations. The worms of the 10th, 15th, and 20th generations are collected for index detection. Interestingly, we found that the fecundity of C. elegans decreased significantly in the exposed group from the 15th generation. At the same time, we found that the growth of C. elegans decreased, motility decreased, and oxidative stress occurred in the exposed group from the 10th generation, which may play roles in the decreased spawning in worms. We preliminarily believe that the microwave energy received by worms leads to oxidative stress, which causes a decrease in the spawning rate, and the underlying mechanism needs to be further studied. © 2022 Bioelectromagnetics Society.

Pulsed High-Peak Power Microwaves at 9.4 GHz Do Not Affect Basic Endpoints in Caenorhabditis elegans.

Because of the extensive application of electromagnetic technology, its health impact on humans has attracted widespread attention. Due to the lack of a model organism with a stable response to electromagnetic waves, the research conclusions on the biological effects of electromagnetic waves have been vague. Therefore, the aim of this study was to investigate the effects of irradiation by pulsed 9.4 GHz high-power microwaves with a peak power density of 2126 W/cm2 using Caenorhabditis elegans. The development, movement, egg production, ROS, and lifespan of C. elegans were detected at different times after irradiation with different repetitive frequencies of 10, 20, and 50 Hz for 30 min. The results indicated that no obvious changes in basic life indices were induced compared with the sham radiation group, but the survival rate of positive control was significantly decreased compared with other groups, which is of interest for microwave protection research based on C. elegans and provides data for updating safety standards with respect to pulsed high-peak power microwave. © 2021 Bioelectromagnetics Society.

Identification of a novel tetracycline resistance gene, tet(63), located on a multiresistance plasmid from Staphylococcus aureus.

OBJECTIVES: To identify and characterize a novel tetracycline resistance gene on a multiresistance plasmid from Staphylococcus aureus SA01 of chicken origin. METHODS: MICs were determined by broth microdilution according to CLSI recommendations. The whole genome sequence of S. aureus SA01 was determined via Illumina HiSeq and Oxford Nanopore platforms followed by a hybrid assembly. The new tet gene was cloned and expressed in S. aureus. The functionality of the corresponding protein as an efflux pump was tested by efflux pump inhibition assays. RESULTS: A novel tetracycline resistance gene, tet(63), was identified on a plasmid in S. aureus SA01. The cloned tet(63) gene was functionally expressed in S. aureus and shown to confer resistance to tetracycline and doxycycline, and a slightly elevated MIC of minocycline. The tet(63) gene encodes a 459 amino acid efflux protein of the major facilitator superfamily that consists of 14 predicted transmembrane helices. The results of efflux pump inhibitor assays confirmed the function of Tet(63) as an efflux protein. The deduced amino acid sequence of the Tet(63) protein exhibited 73.0% identity to the tetracycline efflux protein Tet(K). The plasmid pSA01-tet, on which tet(63) was located, had a size of 25664 bp and also carried the resistance genes aadD, aacA-aphD and erm(C). CONCLUSIONS: A novel tetracycline resistance gene, tet(63), was identified in S. aureus. Its location on a multiresistance plasmid might support the co-selection of tet(63) under the selective pressure imposed by the use of macrolides, lincosamides and aminoglycosides.

Functional expression and purification of recombinant full-length human ATG7 protein with HIV-1 Tat peptide in Escherichia coli.

The human autophagy-related protein ATG7 (hATG7), an E1-like ubiquitin enzyme, activates two ubiquitin-like proteins, LC3 (Atg8) and Atg12, and promotes autophagosome formation. While hATG7 plays an essential role for the autophagy conjugation system, the production of full-length functional hATG7 in bacterial systems remains challenging. Previous studies have demonstrated that the HIV-1 virus-encoded Tat peptide ('GRKKRRQRRR') can increase the yield and solubility of heterologous proteins. Here, functional full-length hATG7 was expressed using the pET28b-Tat expression vector in the Escherichia coli BL21 (DE3) strain. Recombinant hATG7 protein aggregated as inclusion bodies while expressed with widely used prokaryotic expression plasmids. In contrast, the solubility of Tat-tagged hATG7 increased significantly with prolonged time compared to Tat-free hATG7. The recombinant proteins were purified to >90% homogeneity under native conditions with a single step of affinity chromatography purification. The results of in vitro pull-down and LC3B-I lipidation assays showed that Tat-tagged hATG7 directly interacted with LC3B-I and promoted LC3B-I lipidation, suggesting that Tat-tagged hATG7 has significant catalytic activity. Overall, this study provides a novel method for improving the functional expression of full-length hATG7 in bacterial systems by fusion with the Tat peptide, a process which may be applied in future studies of hATG7 structure and function.

Effects of 1.5-GHz high-power microwave exposure on the reproductive systems of male mice.

High-power microwaves (HPMs) have been reported to have hazardous effects on multiple human and animal organs. However, the biological effects of 1.5-GHz HPMs on the reproductive system are not clear. Here, we studied the effects of 1.5 -GHz HPM whole-body exposure on the pathological structure of the testicles and changes in spermatozoa mobility. C57BL/6 mice of groups L, M, and H were exposed to 1.5-GHz HPM fields for two 15-min intervals at the average specific absorption rates of 3, 6, and 12 W/Kg, respectively. The pathological structure of the testicles and spermatozoa, as well as serum testosterone and sperm motility parameters, were evaluated at 6 h, 1 d, 3 d, and 7 d after exposure. As a result, there were no significant pathological or ultrastructural changes in the testicles or spermatozoa and serum testosterone levels. The number of progressively motile spermatozoa, curvilinear velocity, linear velocity, and average path velocity of the exposure group increased at 6 h, decreased at 1 d, and recovered at 3 d. The opposite results were considered a stress response to the thermal effect of the microwaves. Our results indicated that 1.5-GHz HPM whole-body exposure in mice at SARs of 3, 6, and 12 W/Kg for 30 min did not cause obvious damage to the reproductive system.

Characterization of a blaNDM-1-carrying IncHI5 plasmid from Enterobacter cloacae complex of food-producing animal origin.

OBJECTIVES: To characterize an NDM-1-encoding multiresistance IncHI5 plasmid from Enterobacter cloacae complex of chicken origin. METHODS: Carbapenemase genes were detected by PCR and Sanger sequencing. The MICs for the E. cloacae complex isolate and its transformant were determined by the agar dilution and broth microdilution methods. Conjugation and electrotransformation were performed to assess the horizontal transferability of the carbapenemase plasmid. Plasmid DNA was isolated from the transformant and fully sequenced using Illumina HiSeq and PacBio platforms. Plasmid stability was investigated by sequential passages on antibiotic-free medium. A circular intermediate was detected by inverse PCR and Sanger sequencing. RESULTS: Plasmid pNDM-1-EC12 carried a conserved IncHI5 backbone and exhibited an MDR phenotype. All antimicrobial resistance genes were clustered in a single MDR region. Genetic environment analysis revealed that the blaNDM-1 gene was in a novel complex integron, In469. Based on sequence analysis, the blaNDM-1-carrying region was thought to be inserted by homologous recombination. Inverse PCR indicated that an ISCR1-mediated circular intermediate can be formed. Plasmid pNDM-1-EC12 was stably maintained both in the parental strain and the transformant without selective pressure. Comprehensive analysis of IncHI5-type plasmids suggested that they may become another key vehicle for rapid transmission of carbapenemase genes. CONCLUSIONS: To the best of our knowledge, this is the first report of a fully sequenced IncHI5 plasmid recovered from an E. cloacae complex strain of food-producing animal origin. Co-occurrence of blaNDM-1 with genes encoding resistance to other antimicrobial agents on the same IncHI5 plasmid may result in the co-selection of blaNDM-1 and facilitates its persistence and rapid dissemination.

Estimating a Large Travel Time Matrix Between Zip Codes in the United States: A Differential Sampling Approach.

Estimating a massive drive time matrix between locations is a practical but challenging task. The challenges include availability of reliable road network (including traffic) data, programming expertise, and access to high-performance computing resources. This research proposes a method for estimating a nationwide drive time matrix between ZIP code areas in the U.S.-a geographic unit at which many national datasets such as health information are compiled and distributed. The method (1) does not rely on intensive efforts in data preparation or access to advanced computing resources, (2) uses algorithms of varying complexity and computational time to estimate drive times of different trip lengths, and (3) accounts for both interzonal and intrazonal drive times. The core design samples ZIP code pairs with various intensities according to trip lengths and derives the drive times via Google Maps API, and the Google times are then used to adjust and improve some primitive estimates of drive times with low computational costs. The result provides a valuable resource for researchers.

Characterization of a blaIMP-4-carrying plasmid from Enterobacter cloacae of swine origin.

OBJECTIVES: To characterize an MDR blaIMP-4-harbouring plasmid from Enterobacter cloacae EC62 of swine origin in China. METHODS: Plasmid pIMP-4-EC62 from E. cloacae EC62 was transferred by conjugation via filter mating into Escherichia coli J53. Plasmid DNA was extracted from an E. coli J53 transconjugant and sequenced using single-molecule real-time (SMRT) technology. MIC values for both the isolate EC62 and the transconjugant were determined using the broth microdilution and agar dilution methods. Plasmid stability in both the isolate EC62 and the transconjugant was assessed through a series of passages on antibiotic-free media. RESULTS: Plasmid pIMP-4-EC62 is 314351 bp in length, encodes 369 predicted proteins and harbours a novel class 1 integron carrying blaIMP-4 and a group II intron. The blaIMP-4-bearing plasmid belongs to the IncHI2/ST1 incompatibility group. Sequence analysis showed that pIMP-4-EC62 carries four MDR regions and several gene clusters encoding heavy metal resistance. Plasmid pIMP-4-EC62 was stably maintained in both the E. cloacae EC62 isolate and the transconjugant E. coli J53-pIMP-4-EC62 in the absence of selective pressure. Analysis of the evolutionary relatedness of selected IncHI2 plasmids indicates that ST1-type plasmids are key carriers of carbapenemase genes among IncHI2 plasmids. CONCLUSIONS: pIMP-4-EC62 represents the first fully sequenced IncHI2-type blaIMP-4-harbouring plasmid from E. cloacae in China. Co-location of blaIMP-4 with other resistance genes on an MDR plasmid is likely to further accelerate the dissemination of blaIMP-4 by co-selection among bacteria from humans, animals and the environment under the selective pressure of other antimicrobial agents, heavy metals and disinfectants.

Radiofrequency radiation at 2.856 GHz does not affect key cellular endpoints in neuron-like PC12 cells.

To investigate the potential cytotoxicity of radiofrequency (RF) radiation on central nervous system, rat pheochromocytoma (PC12) cells were exposed to 2.856 GHz RF radiation at a specific absorption rate (SAR) of 4 W/kg for 8 h a day for 2 days in 35 mm Petri dishes. During exposure, the real-time variation of the culture medium temperature was monitored in the first hour. Reactive oxygen species (ROS) production, intracellular Ca2+ concentration, and cell apoptosis rate were assessed immediately after exposure by flow cytometry. The results showed that the medium temperature raised about 0.93 °C, but no significant changes were observed in apoptosis, ROS levels or intracellular Ca2+ concentration after treatment. Although several studies suggested that RF radiation does indeed cause neurological effects, this study presented inconsistent results, indicating that 2.856 GHz RF radiation exposure at a SAR of 4 W/kg does not have a dramatic impact on PC12 cells, and suggests the need for further investigation on the key cellular endpoints of other nerve cells after exposure to RF radiation.

Activation of corticotropin releasing factor receptors up regulates collagen production by hepatic stellate cells via promoting p300 expression.

Liver fibrosis is characterized with the over expression and excessive accumulation of extracellular matrix proteins, including collagens. The causative factors in the over production of collagens are not fully understood. This study aims to test a hypothesis that activation of corticotropin releasing factor receptors up regulates the expression of collagen in hepatic stellate cells. In this study, human hepatic stellate cell line, LX-2 cells were cultured. Expression of collagens by LX-2 cells was assessed by real time RT-PCR, Western blotting. The results showed that, upon exposure to urocortin in the culture, LX-2 cells (a human hepatic stellate cell line) increased the expression of collagen IV (Col4) markedly. The exposure to urocortin also enhanced the levels of pTip60, H3K9, RNA polymerase II and forkhead box protein 3 at the collagen promoter locus as well as increase in the expression of Col4 mRNA and protein in the cells. Blocking p300 efficiently suppressed the urocortin-induced Col4 expression in LX-2 cells and unveiled an apoptosis-inducing effect of urocortin. In conclusion, activation of CRF receptors is capable of enforcing the production of Col4 by LX-2 cells via up regulating the p300 pathway, which may contribute to the development of liver fibrosis.

Calibration ruler for CW-EPR distance measurement using diradical molecule of rigid structure.

Many experimental factors and uncontrollable factors may introduce errors in the distance measurement by continuous wave electron paramagnetic resonance. To deal with this problem, several C60 nitroxide diradical adducts with rigid structure and definite molecular dimension were used as distance calibration rulers. Based on the improvement of distance calculation program via adding simulation programs of experimental spectra and dipolar broadening function, respectively, the distance calibration method was developed under different conditions such as different solvent, solution concentration, measuring temperature, and microwave power. As a result, stable distance calibration rulers were established within the range of 8-13 Å. The distance calibration effect was evaluated resulting in a corresponding distance measurement precision of 0.84 Å. The results suggested that the influence of non-dipolar spectral broadening factors could be overcome, and the established experimental and calculation methods were suitable to a wide range of situations. The developed method will ensure more accurate and objective distance measurement in biomacromolecular analysis.

A broadband multi-frequency microwave combined biological exposure setup.

With the rapid popularization of wireless electronic devices, there has been an increasing concern about the impacts of the electromagnetic environment on health. However, most research reports on the biological effects of microwaves have focused on a single frequency point. In reality, people are exposed to complex electromagnetic environments that consist of multiple frequency microwave signals in their daily lives. It is important to investigate whether multi-frequency combined microwave energies have different biological effects compared with single frequency microwave energy. Unfortunately, there are limited reports on this topic due to the lack of suitable platforms for research on multi-frequency microwave energy combined with biological exposure. To address this issue, this study presents a setup that has a very wide working frequency bandwidth and can be compatible with single frequency and multi-frequency microwave combined exposure. Moreover, it can achieve relatively equal exposure to multiple biological samples at any frequency point in the working frequency range, which is crucial for electromagnetic biology research. The experimental results are in good agreement with the simulation results, confirming its capability to facilitate the study of complex electromagnetic environment effects on organisms.

Molecular characteristic of mcr-1 gene in Escherichia coli from aquatic products in Guangdong, China.

OBJECTIVES: Aquatic ecosystems serve as a dissemination pathway and a reservoir of both antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs). This study aimed to determine the prevalence of colistin-resistant mcr-like genes in Enterobacteriales in aquatic products, which may be contribute to the transfer of ARGs in water environments. METHODS: The mcr-1-positive Escherichia coli were recovered from 123 freshwater fish and 34 cultured crocodile cecum samples from 10 farmers' markets in Guangdong, China. Minimum inhibitory concentration (MIC) was determined using the agar dilution method. Genotyping was performed using pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST). Conjugation assay was carried out to investigate the transferability of mcr-1. Genomic information was obtained by whole genome sequencing (WGS) and bioinformatic analysis. RESULTS: Forty-four mcr-1 positive isolates showed co-resistance to tetracycline, trimethoprim/sulfamethoxazole, and gentamicin, while they were all sensitive to tigecycline, meropenem, and amikacin. They were typed into sixteen PFGE clusters. ST10 and ST117 were the most popular sequence types, followed by ST1114. S1-PFGE verified the presence of the mcr-1 gene on plasmids in sizes of ∼60 kb (n = 1) and ∼240 kb (n = 3). Whole genome sequencing-based analysis identified mcr-1 integrated in IncHI2 plasmid (n = 3), IncI2 plasmid (n = 2), and bacterial chromosome in two copies (n = 1). In addition to mcr-1, they carried several other antibiotic resistance genes, such as blaCTX-M-14, fosA3, and aac(6')-Ib-cr. CONCLUSION: These data suggest that aquatic products are an important antibiotic resistance reservoir and highlight possible risks regarding food safety.

The endocannabinoid system is involved in the anxiety-like behavior induced by dual-frequency 2.65/0.8 GHz electromagnetic radiation in mice.

As wireless communication devices gain popularity, concerns about the potential risks of environmental exposure to complex frequency electromagnetic radiation (EMR) on mental health have become a public health issue. Historically, EMR research has predominantly focused on single- frequency electromagnetic waves, neglecting the study of multi-frequency electromagnetic waves, which more accurately represent everyday life. To address these concerns, our study compared the emotional effects of single-frequency and dual-frequency EMR while exploring potential molecular mechanisms and intervention targets. Our results revealed that single-frequency EMR at 2.65 or 0.8 GHz did not induce anxiety-like behavior in mice. However, exposure to dual-frequency EMR at 2.65/0.8 GHz significantly led to anxiety-like behavior in mice. Further analysis of mouse sera revealed substantial increases in corticosterone and corticotrophin releasing hormone levels following exposure to 2.65/0.8 GHz EMR. Transcriptome sequencing indicated a significant decrease in the expression of Cnr1, encoding cannabinoid receptor 1 Type (CB1R), in the cerebral. This finding was consistently verified through western blot analysis, revealing a substantial reduction in CB1R content. Additionally, a significant decrease in the endocannabinoid 2-arachidonoylglycerol was observed in the cerebral cortex. Remarkably, administering the cannabinoid receptor agonist Win55-212-2 significantly alleviated the anxiety-like behavior, and the cannabinoid receptor antagonist AM251 effectively counteracted the anti-anxiety effects of Win55-212-2. In summary, our research confirmed that dual-frequency EMR is more likely to induce anxiety-like behavior in mice than single-frequency EMR, with implications for the hypothalamic-pituitary-adrenal axis and the endocannabinoid system. Furthermore, our findings suggest that Win55-212-2 may represent a novel avenue for researching and developing anti-EMR drugs.

Characterizing the Traveling Oncology Workforce and Its Influence on Patient Travel Burden: A Claims-Based Approach.

PURPOSE: Oncology outreach is a common strategy for extending cancer care to rural patients. However, a nationwide characterization of the traveling workforce that enables this outreach is lacking, and the extent to which outreach reduces travel burden for rural patients is unknown. METHODS: This cross-sectional study analyzed a rural (nonurban) subset of a 100% fee-for-service sample of 355,139 Medicare beneficiaries with incident breast, colorectal, and lung cancers. Surgical, medical, and radiation oncologists were linked to patients using Part B claims, and traveling oncologists were identified by observing hospital service area (HSA) transition patterns. We defined oncology outreach as the provision of cancer care by a traveling oncologist outside of their primary HSA. We used hierarchical gamma regression models to examine the separate associations between patient receipt of oncology outreach and one-way patient travel times to chemotherapy, radiotherapy, and surgery. RESULTS: On average, 9,935 of 39,960 oncologists conducted annual outreach, where 57.8% traveled with low frequency (0-1 outreach visits/mo), 21.1% with medium frequency (1-3 outreach visits/mo), and 21.1% with high frequency (>3 outreach visits/mo). Oncologists provided surgery, radiotherapy, and chemotherapy to 51,715, 27,120, and 5,874 rural beneficiaries, respectively, of whom 2.5%, 6.9%, and 3.6% received oncology outreach. Rural patients who received oncology outreach traveled 16% (95% CI, 11 to 21) and 11% (95% CI, 9 to 13) less minutes to chemotherapy and radiotherapy than those who did not receive oncology outreach, corresponding to expected one-way savings of 15.9 (95% CI, 15.5 to 16.4) and 11.9 (95% CI, 11.7 to 12.2) minutes, respectively. CONCLUSION: Our study introduces a novel claims-based approach for tracking the nationwide traveling oncology workforce and supports oncology outreach as an effective means for improving rural access to cancer care.

Tobramycin-resistant small colony variant mutant of Salmonella enterica serovar Typhimurium shows collateral sensitivity to nitrofurantoin.

The increasing antibiotic resistance poses a significant global health challenge, threatening our ability to combat infectious diseases. The phenomenon of collateral sensitivity, whereby resistance to one antibiotic is accompanied by increased sensitivity to another, offers potential avenues for novel therapeutic interventions against infections unresponsive to classical treatments. In this study, we elucidate the emergence of tobramycin (TOB)-resistant small colony variants (SCVs) due to mutations in the hemL gene, which render S. Typhimurium more susceptible to nitrofurantoin (NIT). Mechanistic studies demonstrate that the collateral sensitivity in TOB-resistant S. Typhimurium SCVs primarily stems from disruptions in haem biosynthesis. This leads to dysfunction in the electron transport chain (ETC) and redox imbalance, ultimately inducing lethal accumulation of reactive oxygen species (ROS). Additionally, the upregulation of nfsA/B expressions facilitates the conversion of NIT prodrug into its active form, promoting ROS-mediated bacterial killing and contributing to this collateral sensitivity pattern. Importantly, alternative NIT therapy demonstrates a significant reduction of bacterial load by more than 2.24-log10 cfu/g in the murine thigh infection and colitis models. Our findings corroborate the collateral sensitivity of S. Typhimurium to nitrofurans as a consequence of evolving resistance to aminoglycosides. This provides a promising approach for treating infections due to aminoglycoside-resistant strains.