Evolution and particle trapping dynamics of circular Pearcey-Airy Gaussian vortex beams in tightly focused systems.

This study investigates the propagation and evolution of self-focusing circular Pearcey-Airy Gaussian vortex beams (CPAGVB) through high numerical aperture objective lenses. CPAGVB demonstrates a unique light field distribution compared to the circular Pearcey vortex beam and circular Airy Gaussian vortex beam. By adjusting optical distribution factors, main radii, and off-axis vortex pair positions, a variety of light field structures can be generated, including asymmetric micro-optical bottles, quasi-flat-top beam micro-optical bottles, and dual optical bottles. The particle trapping performance of CPAGVB is examined, revealing a gradient force eight orders of magnitude larger than its scattering force, up to twice the peak gradient force, and 2.5 times the scattering force of CAGVB. Further analysis of lateral power flow density, spin density vector, and total angular momentum distribution at the focal plane unveils the dynamics of particle motion toward the center. The Gouy phase difference under varying main radii reveals two types of normalized spin density vectors, characterized by helical and oscillating distributions. Additionally, the study examines the two-dimensional polarization ellipse distribution at the focal plane, elucidating the formation of central polarization singularities with axial vortices and the impact of peripheral polarization rearrangement on phase singularities. This research advances the comprehension of CPAGVB's distinctive properties and potential applications in micro-optical systems and particle manipulation.

Experimental generation of the polycyclic tornado circular swallowtail beam with self-healing and auto-focusing.

In this paper, the polycyclic tornado circular swallowtail beam (PTCSB) with autofocusing and self-healing properties is generated numerically and experimentally and their properties are investigated. Compared with the circular swallowtail beam (CSB), the optical distribution of the PTCSB presents a tornado pattern during the propagation. The number of spiral stripes, as well as the orientation of the rotation, can be adjusted by the number and the sign of the topological charge. The Poynting vectors and the orbital angular momentum are employed to investigate the physical mechanism of beam-rotating. In addition, we also introduce a sector-shaped opaque obstacle to investigate the self-healing property of the PTCSB, passing through it with different center angles and discuss the influence of the scaling factor along the propagation direction. Our results may expand the potential applications in the optical spanner and material processing.

Circular Mathieu and Weber autofocusing beams.

In this Letter, the new classes of non-paraxial autofocusing beams are introduced for the first time, to the best of our knowledge. We investigate both numerically and experimentally non-paraxial circular Mathieu and Weber autofocusing beams based on the solutions of the Helmholtz equation in elliptical and parabolic coordinates, respectively. The results show that such beams can significantly shorten the focus distance, and eliminate the intense oscillation effectively after the focusing point. The focal length and the peak intensity can be controlled by tunable parameters. In addition, we further experimentally realize their application of such beams in optical trapping.

Sterilizing Effects of Novel Regimens Containing TB47, Clofazimine, and Linezolid in a Murine Model of Tuberculosis.

TB47, a new drug candidate targeting QcrB in the electron transport chain, has shown a unique synergistic activity with clofazimine and forms a highly sterilizing combination. Here, we investigated the sterilizing effects of several all-oral regimens containing TB47 plus clofazimine and linezolid as a block and the roles of fluoroquinolones and pyrazinamide in them. All these regimens cured tuberculosis within 4 to 6 months in a well-established mouse model, and adding pyrazinamide showed a significant difference in bactericidal effects.

General Strategy to Optimize Gas Evolution Reaction via Assembled Striped-Pattern Superlattices.

Redesigning heterogeneous catalysts so that they can simultaneously integrate the efficiency and durability under reaction environments with respect to gas fuel production, such as hydrogen (H2), oxygen (O2), or carbon monoxide (CO), has proven challenging. In this work, we report the successful template-assisted printing-based assembly of platinum (Pt) nanoparticles (NPs) into striped-pattern (SP) superlattices to produce H2. In comparison to drop-casting flat Pt NPs films, SP superlattices lead to higher mass transference and smaller bubble stretch force, representing a general strategy to improve the efficiency and durability of pre-existed Pt catalysts for the hydrogen evolution reaction (HER), as well as higher current densities than commercial Pt/C, Pt NP films, and many of the other Pt-based or non-Pt-based HER catalysts reported in the literature. The generic nature of template-assisted printing leads to flexibility in the composition, size, and shape of the constituent NPs or molecules, and thus extends such an accelerated technique for producing the oxygen evolution reaction and electrochemical reduction of CO2 to CO.

Engineering of leucine-responsive regulatory protein improves spiramycin and bitespiramycin biosynthesis.

BACKGROUND: Bitespiramycin (BT) is produced by recombinant spiramycin (SP) producing strain Streptomyces spiramyceticus harboring a heterologous 4″-O-isovaleryltransferase gene (ist). Exogenous L-Leucine (L-Leu) could improve the production of BT. The orf2 gene found from the genomic sequence of S. spiramyceticus encodes a leucine-responsive regulatory protein (Lrp) family regulator named as SSP_Lrp. The functions of SSP_Lrp and L-Leu involved in the biosynthesis of spiramycin (SP) and BT were investigated in S. spiramyceticus. RESULTS: SSP_Lrp was a global regulator directly affecting the expression of three positive regulatory genes, bsm23, bsm42 and acyB2, in SP or BT biosynthesis. Inactivation of SSP_Lrp gene in S. spiramyceticus 1941 caused minor increase of SP production. However, SP production of the ΔSSP_Lrp-SP strain containing an SSP_Lrp deficient of putative L-Leu binding domain was higher than that of S. spiramyceticus 1941 (476.2 ± 3.1 µg/L versus 313.3 ± 25.2 µg/L, respectively), especially SP III increased remarkably. The yield of BT in ΔSSP_Lrp-BT strain was more than twice than that in 1941-BT. The fact that intracellular concentrations of branched-chain amino acids (BCAAs) decreased markedly in the ΔSSP_Lrp-SP demonstrated increasing catabolism of BCAAs provided more precursors for SP biosynthesis. Comparative analysis of transcriptome profiles of the ΔSSP_Lrp-SP and S. spiramyceticus 1941 found 12 genes with obvious differences in expression, including 6 up-regulated genes and 6 down-regulated genes. The up-regulated genes are related to PKS gene for SP biosynthesis, isoprenoid biosynthesis, a Sigma24 family factor, the metabolism of aspartic acid, pyruvate and acyl-CoA; and the down-regulated genes are associated with ribosomal proteins, an AcrR family regulator, and biosynthesis of terpenoid, glutamate and glutamine. CONCLUSION: SSP_Lrp in S. spiramyceticus was a negative regulator involved in the SP and BT biosynthesis. The deletion of SSP_Lrp putative L-Leu binding domain was advantageous for production of BT and SP, especially their III components.

Detection of Exhaled Volatile Organic Compounds Improved by Hollow Nanocages of Layered Double Hydroxide on Ag Nanowires.

To detect biomarkers from human exhalation, air flow dynamics on the nanoparticle surface were explored by a surface-enhanced Raman scattering (SERS) sensor. A hollow Co-Ni layered double hydroxide (LDH) nanocage on Ag nanowires (Ag@LDH) was prepared. Ag nanowires provided amplified Raman signals for trace determination; hollow LDH nanocages served as the gaseous confinement cavity to improve capture and adsorption of gaseous analytes. The Raman intensity and logarithmic analyte concentration exhibit an approximately linear relationship; the detection limit of SERS sensors for aldehyde is 1.9×10-9 v/v (1.9 ppb). Various aldehydes in mixed mimetic gas are distinguished by Raman spectra statistical analysis assisted by multivariate methods, including principal component analysis and hierarchical cluster analysis. The information was recorded in a barcode, which can be used for the design and development of a desktop SERS sensor analysis system for large-scale lung cancer detection.

Case-control pharmacogenetic study of HCN1/HCN2 variants and genetic generalized epilepsies.

Epilepsy is a common complex neurological disorder, and some forms are resistant to drug treatment. The HCN1/HCN2 genes encode hyperpolarization-activated cyclic nucleotide-gated channels, which play important roles in the electrophysiology of neurons. We investigated the association between HCN1/HCN2 variants and drug resistance or the risk of genetic generalized epilepsies (GGEs). We used matrix-assisted laser desorption/ionization time-of-flight mass spectrometry to assess nine variants of HCN1/HCN2 in 284 healthy participants and 483 GGEs (279 drug-responsive, 204 drug-resistant). Frequencies of HCN2 rs7255568 and rs3752158 G alleles differed in GGEs and in controls (P = .039, P = .027, respectively). The frequency of HCN2 haplotype (CAC) was higher in patients than controls (P = .046). The frequency of the HCN1 rs10462087 CC+CT genotype was lower in patients with childhood absence epilepsy (CAE) than controls (P = .047). Rs7255568 was associated with the risk of CAE (P = .028) and juvenile myoclonic epilepsy (JME) (P = .02). Rs3752158 was associated with the risk of generalized tonic-clonic seizures, JME, and febrile seizures (all P < .05). The frequency of the HCN2 haplotype (CAC) was higher in patients with JME (P = .015) and in those with febrile seizures (P = .024) than in controls. No significant association was found between HCN1/HCN2 alleles, genotypes or haplotypes, and drug resistance in patients. After Bonferroni's multiple comparisons correction, only the HCN2 rs3752158 C allele and GC+CC genotype frequencies in patients with JME were higher than those in controls (19.2% vs 11.6%, odds ratio (OR) = 1.71, 95% CI = 1.18-2.32), P = .004 < 0.05/9; 36% vs 22.2%, OR = 1.62(1.18-2.23), P = .003 < 0.05/9). Our study suggests that HCN2 rs3752158 is involved in the susceptibility to JME.

Identification of two regulatory genes involved in carbomycin biosynthesis in Streptomyces thermotolerans.

Carbomycins are 16-membered macrolide antibiotics produced by Streptomyces thermotolerans ATCC 11416T. To characterize gene cluster responsible for carbomycin biosynthesis, the draft genome sequences for strain ATCC 11416T were obtained, from which the partial carbomycin biosynthetic gene cluster was identified. This gene cluster was approximately 40 kb in length, and encoding 30 ORFs. Two putative transcriptional regulatory genes, acyB2 and cbmR, were inactivated by insertion of the apramycin resistance gene, and the resulting mutants were unable to produce carbomycin, thus confirming the involvement of two regulatory genes in carbomycin biosynthesis. Overexpression of acyB2 greatly improved the yield of carbomycin; however, overexpression of cbmR blocked carbomycin production. The qPCR analysis of the carbomycin biosynthetic genes in various mutants indicated that most genes were highly expressed in acyB2-overexpressing strains, but few expressed in cbmR-overexpressing strains. Furthermore, acyB2 co-expression with 4″-isovaleryltransferase gene (ist), resulted in efficient biotransformation of spiramycin into bitespiramycin in S. lividans TK24, whereas ist gene regulated by acyB2 and cbmR would cause the lower efficiency of spiramycin biotransformation. These results indicated that AcyB2 was a pathway-specific positive regulator of carbomycin biosynthesis. However, CbmR played a dual role in the carbomycin biosynthesis by acting as a positive regulator, and as a repressor at cbmR high expression levels.

Occurrence of metals, phthalate esters, and perfluoroalkyl substances in cellar water and their relationship with bacterial community in rural areas of China.

Water cellars are traditional rainwater harvesting facilities that have been widely used in rural areas of northwest China. However, there are few reports about the water quality and health risk caused by the cellar water, especially phthalate esters (PAEs) and perfluoroalkyl substances (PFASs). This study investigated and assessed the health risks caused by the metals, PAEs, PFASs and bacterial communities in cellar water. The results showed that the turbidity and total number of bacterial colonies ranged from 4.7 to 58.5 NTU and 5-557 CFU/mL, respectively. The turbidity and total number of bacterial colonies were the main water quality problems. Due to high concentration of Tl (0.005-0.171 µg/L), the samples reached a high level of metal pollution. PAEs showed no non-carcinogenic and carcinogenic risk. The perfluorobutanoic acid (PFBA), perfluorobutanesulfonic acid (PFBS), perfluorooctanoic acid (PFOA), and perfluorooctane sulfonate (PFOS) were the main components of PFASs. PFOA and PFOS reached a moderate risk level in many cellar water samples. Moreover, Tl, Pb, As, PFBA and PFBS could change the bacterial community composition and induce the enrichment of bacterial functions related to human diseases. Besides these parameters, dissolved oxygen (DO) also affected the bacterial functions related to human diseases. Therefore, more attention should be paid to turbidity, DO, Tl, Pb, As, PFOA, PFOS, PFBA and PFBS in the cellar water. These results are meaningful for the water quality guarantee and health protection in rural areas of China.

Efficient Mn(II) removal by biological granular activated carbon filtration.

Sufficient and sustainable manganese(II) removal is a challenging task to prevent Mn-related drinking water discoloration problems. This study investigated Mn(II) removal by granular activated carbon (GAC) filtration under various conditions. The results showed that biological GAC filter columns could reduce Mn(II) from 400 µg/L to 10 µg/L after a short ripening period, while sand filter columns did not show evident Mn(II) removal function. Water quality changes, pretreatment with NaClO and chemogenic MnOx coating on GAC media surface did not influence the Mn(II) removal capacity of GAC filter columns. 16S rRNA gene sequencing showed that the abundance of potential Mn(II)-oxidizing bacteria in the GAC media was similar to that in the sand media. However, qPCR results indicated that GAC media colonized dramatically more biomass than sand media, resulting in highly effective Mn(II) removal by GAC filter columns. Under chlorinated conditions, GAC filtration underperformed sand filtration in Mn(II) removal, although activated carbon has been reported to be capable of catalyzing Mn(II) oxidation by chlorine. Fast chlorine decay in GAC filter columns made it hard to sustain chemical Mn(II) oxidation and thus led to less Mn(II) removal. This study highlighted the advantage of biological GAC filtration over sand filtration in Mn(II) removal.

Ozone and Fenton oxidation affected the bacterial community and opportunistic pathogens in biofilms and effluents from GAC.

Granular activated carbon (GAC) filtration impacts pathogen colonization and bacterial communities in drinking water. However, the effects of ozone and heterogeneous Fenton oxidation on microbial community composition, in particular opportunistic pathogens (OPs), and their metabolic potential in biofilms and effluents from GAC filtration are not fully understood. The results of our pilot-scale test indicated that Fenton-GAC filtration removed more dissolved organic carbon (DOC, 1.25 mg/L) than ozone-GAC filtration (0.98 mg/L). Excitation-emission matrix (EEM) results showed that Fenton-GAC removed more tyrosine-like proteins and fulvic acid-like materials, while ozone-GAC removed more humic acid-like compounds and tryptophan-like proteins. Illumina HiSeq analysis indicated that Curvibacter and Hydrogenophaga dominated in the Fenton-GAC biofilm, while Bradyrhizobium, Aquabacterium and Limnobacter were predominant in the ozone-GAC biofilm. Functional prediction suggested that the microbial functional gene related to glyoxylate and dicarboxylate metabolism (the pathway for carbohydrate metabolism) was higher in the Fenton-GAC biofilm, resulting in higher contents of protein in extracellular polymeric substances (EPS) in the Fenton-GAC biofilm. Therefore, there were fewer bacteria that detached from the biofilm into the water during the Fenton-GAC filtration process. The lower EPS content in the effluents from Fenton-GAC resulted in bacteria, including OPs, being easier to remove by chlorine. However, ozone oxidation removed more bacteria, including different OPs, than Fenton oxidation, which contributed to fewer bacteria and OPs in the effluents from ozone-GAC. Overall, our results provide a Fenton-GAC treatment process to remove DOC and control OPs in drinking water systems, the cost of which was comparable to that of ozone-GAC.

High efficiency electrochemical disinfection of Pseudomons putida using electrode of orange peel biochar with endogenous metals.

The electrochemical disinfection efficiency of Pseudomons putida was studied using ruthenium iridium coated titanium (RICT) electrode as anode and carbonized orange peel biochar (OPB) or graphite as the cathode. The results indicated that RICT/OPB system induced 6.5 and 7.0 log of P. putia inactivation after 60 s at 2 V and 45 s at 10 V, respectively. RICT/OPB system showed better efficiency than RICT/graphite system. The energy consumption of OPB cathode (17.5 Wh m-3 per log) was significantly lower than that of graphite cathode (23.09 Wh m-3 per log). Both anode and cathode played great roles on the disinfection. The anode absorbed electric energy to generate electrical hole, which can oxidize chloride ions to chlorine free radicals. The continuous porous structure of OPB can provide more adsorption sites and reduce electrolyte transport resistance, resulting in more Cl· production. Moreover, P. putia was much easier adsorbed to the anode surface in the RICT/OPB system because of the stronger electrostatic repulsion between cells and OPB cathode. As a result, P. putia was more easily inactivated by the Cl· produced on the anode. Besides chlorine active species, superoxide radical (O2·ï¹£) produced on surface of cathode may also result in P. putia inactivation. The endogenous CuO in OPB can induce persistent free radicals (PFRs) production during pyrosis process. O2·ï¹£ can be produced by O2 activation through the function of Cu2O/CuO and PFRs existed in OPB cathode. The more superoxide radical production led to the better disinfection effect than the graphite cathode. As a consequence, OPB electrode showed high efficiency electrochemical disinfection of P. putida.

Rural-urban differences in prevalence of and risk factors for refractive errors among school children and adolescents aged 6-18 years in Dalian, China.

Purpose: To assess the prevalence of refractive errors (REs) in school children aged 6-18 years in urban and rural settings in Dalian, Northeast of China. Methods: This is a school-based cross-sectional survey using multi-stage randomization technique. Six- to eighteen-year-old school children from elementary schools, junior and senior high schools from a rural area and an urban area in Dalian were included in December 2018. All subjects underwent a comprehensive questionnaire and eye examination. Results: A total of 4,522 school children with 6-18 years of age were investigated. The age, gender-adjusted prevalence of myopia, and anisometropia were 82.71 and 7.27% among the urban students as compared to 71.76% and 5.41% among the rural ones (OR = 1.80, 95 % CI = 1.53 - 2.11, P < 0.001; OR = 1.29, 95 % CI = 1.00-1.67, P = 0.049), respectively. The hyperopia was less common in urban students than in rural ones (5.63 vs. 10.21%; OR = 0.54, 95 % CI: 0.43-0.67, P < 0.001). However, there was no significant difference in prevalence of astigmatism between urban (46.07%) and rural (44.69%) participants (OR = 0.96, 95 % CI: 0.84-1.10, P = 0.559). The differences on prevalence of REs were attributed to different social-demographic and physiologic factors. Conclusions: The students from urban settings are more likely to have myopia and anisometropia but less likely to have hyperopia than their rural counterparts. Although considerable attention had been paid to controlling REs, it is necessary to further consider the urban-rural differences in REs.

Arabinosyltransferase C Mediates Multiple Drugs Intrinsic Resistance by Altering Cell Envelope Permeability in Mycobacterium abscessus.

Mycobacterium abscessus is an emerging human pathogen leading to significant morbidity and even mortality, intrinsically resistant to almost all the antibiotics available and so can be a nightmare. Mechanisms of its intrinsic resistance remain not fully understood. Here, we selected and confirmed an M. abscessus transposon mutant that is hypersensitive to multiple drugs including rifampin, rifabutin, vancomycin, clofazimine, linezolid, imipenem, levofloxacin, cefoxitin, and clarithromycin. The gene MAB_0189c encoding a putative arabinosyltransferase C was found to be disrupted, using a newly developed highly-efficient strategy combining next-generation sequencing and multiple PCR. Furthermore, selectable marker-free deletion of MAB_0189c recapitulated the hypersensitive phenotype. Disruption of MAB_0189c resulted in an inability to synthesize lipoarabinomannan and markedly enhanced its cell envelope permeability. Complementing MAB_0189c or M. tuberculosis embC restored the resistance phenotype. Importantly, treatment of M. abscessus with ethambutol, a first-line antituberculosis drug targeting arabinosyltransferases of M. tuberculosis, largely sensitized M. abscessus to multiple antibiotics in vitro. We finally tested activities of six selected drugs using a murine model of sustained M. abscessus infection and found that linezolid, rifabutin, and imipenem were active against the MAB_0189c deletion strain. These results identified MAB_0189 as a crucial determinant of intrinsic resistance of M. abscessus, and optimizing inhibitors targeting MAB_0189 might be a strategy to disarm the intrinsic multiple antibiotic resistance of M. abscessus. IMPORTANCE Mycobacterium abscessus is intrinsically resistant to most antibiotics, and treatment of its infections is highly challenging. The mechanisms of its intrinsic resistance remain not fully understood. Here we found a transposon mutant hypersensitive to a variety of drugs and identified the transposon inserted into the MAB_0189c (orthologous embC coding arabinosyltransferase, EmbC) gene by using a newly developed rapid and efficient approach. We further verified that the MAB_0189c gene played a significant role in its intrinsic resistance by decreasing the cell envelope permeability through affecting the production of lipoarabinomannan in its cell envelope. Lastly, we found the arabinosyltransferases inhibitor, ethambutol, increased activities of nine selected drugs in vitro. Knockout of MAB_0189c made M. abscessus become susceptible to 3 drugs in mice. These findings indicated that potential powerful M. abscessus EmbC inhibitor might be used to reverse the intrinsic resistance of M. abscessus to multiple drugs.

Ultra-short-course and intermittent TB47-containing oral regimens produce stable cure against Buruli ulcer in a murine model and prevent the emergence of resistance for Mycobacterium ulcerans.

Buruli ulcer (BU), caused by Mycobacterium ulcerans, is currently treated with rifampin-streptomycin or rifampin-clarithromycin daily for 8 weeks recommended by World Health Organization (WHO). These options are lengthy with severe side effects. A new anti-tuberculosis drug, TB47, targeting QcrB in cytochrome bc1:aa3 complex is being developed in China. TB47-containing regimens were evaluated in a well-established murine model using an autoluminescent M. ulcerans strain. High-level TB47-resistant spontaneous M. ulcerans mutants were selected and their qcrB genes were sequenced. The in vivo activities of TB47 against both low-level and high-level TB47-resistant mutants were tested in BU murine model. Here, we show that TB47-containing oral 3-drug regimens can completely cure BU in ≤2 weeks for daily use or in ≤3 weeks given twice per week (6 doses in total). All high-level TB47-resistant mutants could only be selected using the low-level mutants which were still sensitive to TB47 in mice. This is the first report of double mutations in QcrB in mycobacteria. In summary, TB47-containing regimens have promise to cure BU highly effectively and prevent the emergence of drug resistance. Novel QcrB mutations found here may guide the potential clinical molecular diagnosis of resistance and the discovery of new drugs against the high-level resistant mutants.

Corrigendum: Scorpion Venom Analgesic Peptide, BmK AGAP Inhibits Stemness and Epithelial-Mesenchymal Transition by Down-Regulating PTX3 in Breast Cancer.

[This corrects the article DOI: 10.3389/fonc.2019.00021.].

Nanomaterial-based gas sensors used for breath diagnosis.

Gas-sensing applications commonly use nanomaterials (NMs) because of their unique physicochemical properties, including a high surface-to-volume ratio, enormous number of active sites, controllable morphology, and potential for miniaturisation. NM-based gas sensors, as a noninvasive, real-time technique, are a promising candidate for monitoring human breath. This review focuses on NM-based gas sensors used for breath diagnosis. First we describe some representative biomarkers of diseases that are detectable in breath and requirements for breath sensors. Then we review electrical, optical and mass-sensitive gas sensors in terms of these performance requirements, together with describing the detection capability of these sensors for trace concentrations of biomarkers and their initial attempts to diagnose disease. Moreover, we discuss breath sensor platforms with a multivariable sensing system, wireless communication and breath sampling, essential for predictive, preventive, personalised, and participatory ("P4") medicine. Finally, we conclude with problems and challenges associated with the selectivity, humidity and validation of breath sensors. We hope that this article will inspire the development of high-performance gas sensors based on novel NMs.

TB47 and clofazimine form a highly synergistic sterilizing block in a second-line regimen for tuberculosis in mice.

Multidrug-resistant tuberculosis (MDR-TB) remains a serious public health threat worldwide. To date, the anti-TB activity of TB47 (T), an imidazopyridine amide class of antibiotics targeting QcrB in the electron transport chain, has not been systematically evaluated, especially in a new regimen against MDR-TB. This study employed both macrophage infection and a mouse model to test the activity of T alone or in combination with other antimicrobial agents. Different regimens containing amikacin (A), levofloxacin (L), ethambutol (E), and pyrazinamide (Z) + clofazimine (C)/T were evaluated in the mouse model. The bacterial burdens of mice from different groups were monitored at different time points while relapse was assessed 6 months after treatment cessation. Colonies obtained at relapse underwent drug susceptibility testing. We found that T exhibited highly synergistic bactericidal activity with C in all models. Adding T to ALEZC might shorten the MDR-TB treatment duration from ≥ 9 months to ≤ 5months, as five months of treatment with ALEZCT achieved zero relapse rates in 2 animal experiments. These findings indicate that T exhibits a highly synergistic sterilizing activity when combined with C. All isolates from relapsing mice remained sensitive to each drug, suggesting that the relapse was not due to drug resistance but rather associated with the type of regimen.

Prevalence and molecular characterization of amikacin resistance among Mycobacterium tuberculosis clinical isolates from southern China.

OBJECTIVES: Amikacin is the only second-line injectable antituberculosis (anti-TB) drug still recommended for multidrug-resistant tuberculosis (MDR-TB) treatment when a short MDR-TB regimen is designed. Mutations in rrs and eis are reported to be associated with resistance to amikacin. In this study, we investigated the incidence of rrs, eis, tap and whiB7 mutations in amikacin-resistant Mycobacterium tuberculosis clinical isolates to find the proportion of different mutations related to amikacin resistance. METHODS: A total of 395 clinical isolates of M. tuberculosis were used for phenotypic drug susceptibility testing (DST) to 10 drugs with the Löwenstein-Jensen (L-J) method. We sequenced rrs, eis, tap and whiB7 genes in 178 M. tuberculosis clinical isolates (89 amikacin-resistant isolates and 89 of 306 amikacin-susceptible isolates). RESULTS: Our data showed that 22.53% (89/395) M. tuberculosis clinical isolates were resistant to amikacin. Of the 89 amikacin-resistant isolates, 89.89% (80/89) were MDR-TB, of which 12.36% (11/89) were pre-extensively drug-resistant TB (pre-XDR-TB) and 77.53% (69/89) were XDR-TB. The rrs mutations were found in 82% (73/89) in amikacin-resistant M. tuberculosis clinical isolates. The A1401G alteration in the rrs gene was the most dominant mutation (80.90%; 72/89). Five mutations were detected as new in rrs, tap and whiB7. Notably, 13.48% (12/89) amikacin-resistant isolates had no known mutation in these genes. CONCLUSIONS: Our data reveal that the rrs mutation is a predominant molecular marker of amikacin resistance in southern China. Analysis of the rrs gene mutations will significantly reduce the time and cost to diagnose amikacin resistance in TB patients. Other unknown amikacin resistance mechanism(s) exist.