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Colistin is considered the last-line antimicrobial for the treatment of multidrug-resistant gram-negative bacterial infections. The emergence and spread of superbugs carrying the mobile colistin resistance gene ( mcr ) have become the most serious and urgent threat to healthcare. Here, we discover that silver (Ag + ), including silver nanoparticles, could restore colistin efficacy against mcr -positive bacteria. We show that Ag + inhibits the activity of the MCR-1 enzyme via substitution of Zn 2+ in the active site. Unexpectedly, a tetra-silver center was found in the active-site pocket of MCR-1 as revealed by the X-ray structure of the Ag-bound MCR-1, resulting in the prevention of substrate binding. Moreover, Ag + effectively slows down the development of higher-level resistance and reduces mutation frequency. Importantly, the combined use of Ag + at a low concentration with colistin could relieve dermonecrotic lesions and reduce the bacterial load of mice infected with mcr -1–carrying pathogens. This study depicts a mechanism of Ag + inhibition of MCR enzymes and demonstrates the potentials of Ag + as broad-spectrum inhibitors for the treatment of mcr -positive bacterial infection in combination with colistin.

The emergence of New Delhi metallo-beta-lactamase (NDM-1) has become a major health threat to clinical managements of gram-negative bacteria infections. A novel incompatibility group X3 plasmid (IncX3) pNDM-HN380 carrying bla NDM-1 has recently been found to epidemiologically link with multiple geographical areas in China. In this paper, we studied the metabolic responses of host bacteria E. coli J53 upon introduction of pNDM-HN380. A reduction of bacterial motility was observed in J53/pNDM-HN380. We profiled the RNA repertoires of the transconjugants and found a downregulation of genes involved in flagella and chemotaxis metabolic pathways at logarithmic (log) phase. We also identified a novel intragenic region (IGR) small RNA plas2. The plasmid-transcribed sRNA IGR plas2 was further characterized as a regulator of fucR which controls the fucose metabolism. By knockdown of IGR plas2 using an antisense decoy, we managed to inhibit the formation of bacterial biofilm of the host. Our study demonstrated a potential way of utilizing plasmid-transcribed sRNA against infectious bacteria.

Six imported pigs originating from Guangdong, Henan, and Hunan provinces in China during October 2015 to February 2017 were cultured and found to be positive for meropenem-resistant Escherichia coli The samples yielded 9 E. coli isolates of diverse sequence types carrying bla NDM-5 on IncX3 (8 isolates from 5 farms) or IncFII (1 isolate from 1 farm) plasmids. The mcr-1 gene was coharbored by 4 isolates. The IncX3 plasmids (∼46 kb) carrying bla NDM-5 were identical or nearly identical to each other., (Copyright © 2018 American Society for Microbiology.)

Aminoglycoside resistance determinants among 188 aminoglycoside-resistant blood culture Escherichia coli isolates from a tertiary hospital in Hong Kong, from 2004 to 2010 were investigated. Overall, 91% had aac(3)-II, 12.2% had aac(6')-Ib/Ib-cr, and 5.4% had the methylase genes (rmtB, armA). Aminoglycoside-resistant isolates with aac(')-Ib/Ib-cr, rmtB, and armA often had coresistance to multiple other antibiotics., (Copyright © 2014. Published by Elsevier B.V.)

Increasing consumption of nitrofurantoin (NIT) for treatment of acute uncomplicated urinary tract infections (UTI) highlights the need to monitor emerging NIT resistance mechanisms. This study investigated the molecular epidemiology of the multidrug-resistant efflux gene oqxAB and its contribution to nitrofurantoin resistance by using Escherichia coli isolates originating from patients with UTI (n = 205; collected in 2004 to 2013) and food-producing animals (n = 136; collected in 2012 to 2013) in Hong Kong. The oqxAB gene was highly prevalent among NIT-intermediate (11.5% to 45.5%) and -resistant (39.2% to 65.5%) isolates but rare (0% to 1.7%) among NIT-susceptible (NIT-S) isolates. In our isolates, the oqxAB gene was associated with IS26 and was carried by plasmids of diverse replicon types. Multilocus sequence typing revealed that the clones of oqxAB-positive E. coli were diverse. The combination of oqxAB and nfsA mutations was found to be sufficient for high-level NIT resistance. Curing of oqxAB-carrying plasmids from 20 NIT-intermediate/resistant UTI isolates markedly reduced the geometric mean MIC of NIT from 168.9 μg/ml to 34.3 μg/ml. In the plasmid-cured variants, 20% (1/5) of isolates with nfsA mutations were NIT-S, while 80% (12/15) of isolates without nfsA mutations were NIT-S (P = 0.015). The presence of plasmid-based oqxAB increased the mutation prevention concentration of NIT from 128 μg/ml to 256 μg/ml and facilitated the development of clinically important levels of nitrofurantoin resistance. In conclusion, plasmid-mediated oqxAB is an important nitrofurantoin resistance mechanism. There is a great need to monitor the dissemination of this transferable multidrug-resistant efflux pump., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

This study investigated 248 extended-spectrum β-lactamase-producing Escherichia coli isolates from 2012 to 2013 for hybrid blaCTX-M genes. blaCTX-M genes were detected in 228 isolates of which 14 isolates were hybrid blaCTX-M positive (6 blaCTX-M-123, 6 blaCTX-M-64, and 2 blaCTX-M-132). The 14 hybrid blaCTX-M-carrying isolates (8 from chickens, 2 each from pigs and cattle, 1 each from dog and rodent) were genetically diverse. All but 2 hybrid blaCTX-M were carried on IncI1 (5 blaCTX-M-123) and IncI2 (6 blaCTX-M-64 and one blaCTX-M-132) plasmids. Our IncI1 and IncI2 plasmids had pHNAH4-1-like and pHN1122-1-like restriction fragment length polymorphism patterns, respectively. Genetic relatedness of the plasmids to pHNAH4-1 and pHN1122-1 were confirmed by complete sequencing of 3 plasmids, pCTXM123_C0996, pCTXM64_C0967, and pCTXM132_P0421. Plasmids closely related to pHNAH4-1 and pHN1122-1 and carrying different blaCTX-M alleles have been reported from multiple geographic areas in China previously. The findings highlighted the wide dissemination of hybrid blaCTX-M variants in different parts of China., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Previous work on the subclones within Escherichia coli ST131 predominantly involved isolates from Western countries. This study assessed the prevalence and antimicrobial resistance attributed to this clonal group. A total of 340 consecutive, non-duplicated urinary E. coli isolates originating from four clinical laboratories in Hong Kong in 2013 were tested. ST131 prevalence among the total isolates was 18.5 % (63/340) and was higher among inpatient isolates (23.0 %) than outpatient isolates (11.8 %, P<0.001), and higher among isolates from patients aged ≥65 years than from patients aged 18-50 years and 51-64 years (25.4 vs 3.4 and 4.0 %, respectively, P<0.001). Of the 63 ST131 isolates, 43 (68.3 %) isolates belonged to the H30 subclone, whereas the remaining isolates belonged to H41 (n = 17), H54 (n = 2) and H22 (n = 1). All H30 isolates were ciprofloxacin-resistant, of which 18.6 % (8/43) belonged to the H30-Rx subclone. Twenty-six (41.3 %) ST131 isolates were ESBL-producers, of which 19 had blaCTX-M-14 (12 non-H30-Rx, two H30-Rx and five H41), six had blaCTX-M-15 (five non-H30-Rx and one H30-Rx) and one was blaCTX-M-negative (H30). In conclusion, ST131 accounts for a large share of the antimicrobial-resistant E. coli isolates from geriatric patients. Unlike previous reports, ESBL-producing ST131 strains mainly belonged to non-H30-Rx rather than the H30-Rx subclone, with blaCTX-M-14 as the dominant enzyme type., (© 2015 The Authors.)

This territory-wide study investigated the occurrence of faecal carriage of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli among wild rodents from the 18 districts in Hong Kong. Individual rectal swabs were obtained from the trapped animals and cultured in plain and selective media. A total of 965 wild rodents [148 chestnut spiny rats (Niviventer fulvescens), 326 Indo-Chinese forest rats (Rattus andamanensis), 452 brown rats (Rattus norvegicus) and 39 black rats (Rattus rattus)] were sampled. ESBL carriage was 0 % in chestnut spiny rats, 0.6 % in Indo-Chinese forest rats, 7.7 % in black rats and 13.9 % in brown rats. Among brown rats, the prevalence of ESBL carriage differed markedly by geographical location: absent in two districts, low (7-10 %) in six districts, moderate (11-19 %) in seven districts and high (21-50 %) in three districts. Nonetheless, there was no correlation between the prevalence of ESBL in brown rats and human population density in the 18 districts. CTX-M-type enzymes were detected in 92.0 % of the ESBL-producing isolates, of which 83.1 % were resistant to three or more non-β-lactam drugs. The CTX-M producing isolates were genetically diverse but a large proportion (47.8 %) were included in six successful clones that are strongly associated with human diseases and CTX-M dissemination, viz. sequence type complex [STC]10/phylogroup A, STC23/phylogroup B1, STC38/phylogroup D, STC155/phylogroup B1, ST405/phylogroup D and ST131/phylogroup B2. In conclusion, our results show that brown rats often carry potentially zoonotic clones of CTX-M producing, multidrug-resistant E. coli. The potential for rats to be a source of CTX-M producing E. coli for humans deserves further consideration., (© 2015 The Authors.)

Few studies have described how an expanding elderly population influences the burden of antimicrobial resistance in micro-organisms. This study aimed to investigate trends in age-stratified extended-spectrum β-lactamase (ESBL)-positive Escherichia coli metrics in relation to an ageing population. The antimicrobial resistance database of E. coli from a healthcare region in Hong Kong from 2003 to 2012 was retrospectively reviewed. Future trends in age-stratified ESBL metrics were predicted up to 2022. Susceptibility results of clinical E. coli isolates from patients aged 0-74 years (n = 17 853) and aged ≥75 years (n = 17 047) were analysed. For the period 2003-2012, 23.7 % of the hospital admissions were of patients aged ≥75 years. However, approximately half of the annual ESBL-positive E. coli isolates were recovered from patients aged ≥75 years, being 55.0 % (233/424) in 2003 and 56.0 % (639/1142) in 2012. During this period of time, the annual prevalence and cumulative incidence of ESBL-positive E. coli in patients aged ≥75 years were significantly higher than in patients aged 0-74 years. From 2012-2022, it is predicted that ESBL-positive E. coli prevalence among patients aged 0-74 years and ≥75 years would increase from 25.4 % to 50.2 % and from 30.8 % to 70.0 %, respectively. In 2022, the predicted ESBL-positive E. coli cumulative incidence would be 63.7 per 10 000 admissions and 178.7 per 10 000 admissions among patients aged 0-74 years and ≥75 years, respectively. In conclusion, a rapidly expanding elderly population would substantially add to the burden of ESBL., (© 2014 The Authors.)

This study investigated the prevalence of IncX plasmid subtypes in commensal and pathogenic Escherichia coli isolates and the biological features of the IncX4 subtype. Two hundred and twenty-five E. coli isolates from multiple sources (47 chickens, 41 pigs, 30 cattle and 107 humans) obtained during the period 2006-2012 were tested for the presence of IncX1 to IncX5. Overall, the prevalence of IncX plasmids in chicken, pig, cattle and human isolates were 21.2 % (10/47), 19.5 % (8/41), 3.3 % (1/30) and 4.8 % (5/107), respectively. IncX4 was the most common subtype, followed by IncX1 and IncX3, while no IncX2 or IncX5 were found. Seven out of 16 (43.8 %) IncX4 plasmids were found to carry blaCTX-M genes and six of them originating from different host sources (four chickens, one pig and one human) had identical or highly similar RFLP patterns. Three IncX4 plasmids carrying blaCTX-M from different host sources were investigated further. It was found that the IncX4 plasmids had little effect on bacterial host growth parameters after their introduction to J53 recipients. Conjugation experiments demonstrated that the IncX4 plasmids could be efficiently transferred at 30-42 °C at rates which were generally 10(2)-10(5)-fold higher than those for the epidemic IncFII plasmid carrying blaCTX-M (pHK01). In conclusion, the IncX plasmids are more common than previously recognized. The efficient transfer of IncX4 plasmid at different temperatures and the lack of fitness burden on bacterial hosts highlight the ability of this plasmid replicon to be an important vehicle for dissemination of antimicrobial resistance., (© 2014 The Authors.)

A total of 1878 non-duplicate clinical Escherichia coli isolates (comprising 1711 urinary isolates and 167 blood-culture isolates), which were collected from multiple centres in Hong Kong during 1996-2008, were used to investigate the prevalence and molecular epidemiology of plasmid-mediated fosfomycin (fos) resistance genes. Eighteen of the 1878 clinical E. coli isolates were fosfomycin resistant, of which six were fosA3 positive and two were positive for another fosA variant (designated fosKP96). No isolates had the fosC2 gene. The clones of the eight isolates were diverse: sequence type (ST) 95 (n = 2), ST118 (n = 1), ST131 (n = 1), ST617 (n = 1), ST648 (n = 1), ST1488 (n = 1) and ST2847 (n = 1). In the isolates, fosA3 and blaCTX-M genes were co-harboured on conjugative plasmids with F2:A-:B- (n = 2), N (n = 1), F-:A-:B1 and N (n = 1) and untypable (n = 2) replicons. Both fosKP96-carrying plasmids belonged to replicon N. RFLP analysis showed that the two F2:A-:B- plasmids carrying fosA3 and blaCTX-M-3 genes shared the same pattern. Complete sequencing of one of the two F2:A-:B- plasmids, pFOS-HK151325 (69 768 bp) demonstrated it to be >99 % identical to the previously sequenced plasmid pHK23a originating from a pig E. coli isolate in the same region. This study demonstrated the dissemination of fosA3 genes in diverse E. coli clones on multiple blaCTX-M-carrying plasmid types, of which F2:A-:B- plasmids closely related to pHK23a were shared by isolates from human and animal sources.

Objectives: This study assessed the impact of discordant empirical antibiotic therapy on the outcome of bacteremia caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli., Methods: The clinical features and outcomes of a cohort of patients hospitalized with ESBL E. coli bacteremia between 2007 and 2008 were retrospectively reviewed. The effect of different antimicrobial regimens on patient outcomes was analyzed., Results: ESBL E. coli accounted for 24.2% (207/857) of E. coli bacteremia cases. The urinary tract (43.6%) was the most common source of infection, followed by the hepatobiliary tract (23.0%). Discordant empirical antibiotic therapy was given to 52.0% patients. Admission to the intensive care unit was associated with the use of a carbapenem as empirical antibiotic therapy (p<0.001). Univariate analysis revealed no significant differences in 30-day mortality rates between patients receiving concordant and discordant empirical antibiotic therapy (23.5% vs. 19.8%, p=0.526), carbapenem and non-carbapenem empirical antibiotic therapy (29.8% vs. 19.1%, p=0.118), beta-lactam/beta-lactam inhibitor combinations (BLBLIs) and non-BLBLIs empirical antibiotic therapy (20.3% vs. 22.3%, p=0.734), cephalosporin and non-cephalosporin empirical antibiotic therapy (19.7% vs. 22.6%, p=0.639), and fluoroquinolone and non-fluoroquinolone empirical antibiotic therapy (8.3% vs. 22.4%, p=0.251). The findings were confirmed by multivariate analysis., Conclusions: Despite a high proportion of discordant empirical antibiotic therapy, ESBL production had little effect on 30-day mortality. Whether the observation can be applied to different ESBL types is unknown and warrants further study., (Copyright © 2012 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

This study assessed the temporal changes in the molecular epidemiology of bacteremic Escherichia coli isolates producing CTX-M-14 in Hong Kong. Blood isolates from 1996 to 1998 (period 1, n = 50) and 2007 to 2008 (period 2, n = 117) were investigated by molecular methods. CTX-M-type ESBL was carried by 98.2% (164/167) of the isolates. In both periods, the CTX-M-9 group and CTX-M-14 allele were the predominant ESBL type. The major clones were found to change from ST68 and ST405 in period 1 to ST131, ST69, and ST12 in period 2. Among 65 CTX-M-14-producing plasmids investigated further, 54 had the FII replicon. Replicon sequence typing and plasmid polymerase chain reaction-restriction fragment length polymorphism showed that 79.6% (43/54) of the FII plasmid subset was similar to the completely sequenced plasmid, pHK01 (human urine, Hong Kong, 2004). These pHK01-like plasmids were found to have spread to the major clones (ST68, ST405, and ST131) and multiple singleton isolates of all 4 phylogenetic groups., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: The emergence of plasmid-mediated carbapenemases, such as NDM-1 in Enterobacteriaceae is a major public health issue. Since they mediate resistance to virtually all β-lactam antibiotics and there is often co-resistance to other antibiotic classes, the therapeutic options for infections caused by these organisms are very limited., Methodology: We characterized the first NDM-1 producing E. coli isolate recovered in Hong Kong. The plasmid encoding the metallo-β-lactamase gene was sequenced., Principal Findings: The plasmid, pNDM-HK readily transferred to E. coli J53 at high frequencies. It belongs to the broad host range IncL/M incompatibility group and is 88803 bp in size. Sequence alignment showed that pNDM-HK has a 55 kb backbone which shared 97% homology with pEL60 originating from the plant pathogen, Erwina amylovora in Lebanon and a 28.9 kb variable region. The plasmid backbone includes the mucAB genes mediating ultraviolet light resistance. The 28.9 kb region has a composite transposon-like structure which includes intact or truncated genes associated with resistance to β-lactams (bla(TEM-1), bla(NDM-1), Δbla(DHA-1)), aminoglycosides (aacC2, armA), sulphonamides (sul1) and macrolides (mel, mph2). It also harbors the following mobile elements: IS26, ISCR1, tnpU, tnpAcp2, tnpD, ΔtnpATn1 and insL. Certain blocks within the 28.9 kb variable region had homology with the corresponding sequences in the widely disseminated plasmids, pCTX-M3, pMUR050 and pKP048 originating from bacteria in Poland in 1996, in Spain in 2002 and in China in 2006, respectively., Significance: The genetic support of NDM-1 gene suggests that it has evolved through complex pathways. The association with broad host range plasmid and multiple mobile genetic elements explain its observed horizontal mobility in multiple bacterial taxa.

A bacterial collection (n=249) obtained in Hong Kong from 2002 to 2004 was used to investigate the molecular epidemiology of aminoglycoside resistance among Escherichia coli isolates from humans and food-producing animals. Of these, 89 isolates were gentamicin-sensitive (human n=60, animal n=29) and 160 isolates were gentamicin-resistant (human n=107, animal n=53). Overall, 84.1% (90/107) and 75.5% (40/53) of the gentamicin-resistant isolates from human and animal sources, respectively, were found to possess the aacC2 gene. The aacC2 gene for 20 isolates (10 each for human and animal isolates) was sequenced. Two alleles were found that were equally distributed in human and animal isolates. PFGE showed that the gentamicin-resistant isolates exhibited diverse patterns with little clonality. In some isolates, the aacC2 gene was encoded on large transferable plasmids of multiple incompatibility groups (IncF, IncI1 and IncN). An IncFII plasmid of 140 kb in size was shared by one human and three animal isolates. In summary, this study showed that human and animal isolates share the same pool of resistance genes.

A prospective multicenter study was conducted to assess the epidemiology of antimicrobial resistance among uropathogens causing uncomplicated cystitis. Adult women with clinical diagnosis of uncomplicated cystitis were enrolled from 54 participating centers distributed all over Hong Kong during 2006 to 2008. A positive urine culture was found in 59.5% (352/592) patients. The patients had mean age of 44.9 years, and most (89.2%) were otherwise healthy. The most prevalent causative organism was Escherichia coli (77%), followed by other Enterobacteriaceae (14.2%), staphylococci (5.1%), and other Gram-positive bacteria (3.7%). The resistance rates of E. coli to co-trimoxazole and ciprofloxacin were 29.5% and 12.9%, respectively, and 14 isolates (5.2%) were confirmed as extended-spectrum beta-lactamase (ESBL) producers. Of the ESBL producers, molecular studies showed CTX-M-14, CTX-M-24, or CTX-M-9. Nitrofurantoin and fosfomycin were active against >90% of the isolates, regardless of resistance phenotypes for other drugs. Pulsed-field gel electrophoresis of representative isolates showed that the antibiotic-resistant strains were genetically diverse. Patients with history of recent antibiotic use were significantly more likely to have infection by E. coli with co-trimoxazole resistance (odds ratio [OR], 2.8; 95% confidence interval [CI], 1.4-5.7; P = 0.003) and ciprofloxacin resistance (OR, 2.5; 95% CI, 1.1-5.8; P = 0.03). Knowledge of the resistance data and risk factors could inform better use of antibiotics for empiric therapy for acute uncomplicated cystitis.

We investigated the occurrence and diversity of extended-spectrum beta-lactamase (ESBL) enzymes among antibiotic-resistant Escherichia coli and Klebsiella pneumoniae isolates obtained from human feces. All ESBL-positive isolates were characterized at the molecular level by polymerase chain reaction, sequencing and pulsed-field gel electrophoresis (PFGE). Eight of 46 antibiotic-resistant E. coli (6 from children and 2 from adults) and 4 of 8 K. pneumoniae (all from adults) isolates were found to be ESBL-positive by the double-disk synergy test. Seven isolates were found to have CTX-M-14, 2 each had CTX-M-24 and CTX-M-38, and 1 had CTX-M-9. In addition, 8 isolates were found to carry TEM-1b or TEM-1c. No SHV-type enzyme was found among the E. coli strains. In 9 strains, the plasmidic bla(CTX-M) determinants were transferable to E. coli by conjugation. Analysis by PFGE showed evidence of clonal and non-clonal spread. The present study shows fecal carriage of organisms producing bla(CTX-M) determinants and underscores the role that commensals could play as a reservoir for their dissemination.

This study evaluated the antimicrobial resistance profile of outpatient urinary Escherichia coli isolated from women obtained throughout Hong Kong during 2004-2005. Of 1067 single patient isolates analyzed, 60.1% were resistant to ampicillin, 34% were resistant to co-trimoxazole, and 22.1% were resistant to ciprofloxacin. Thirty-four (6.6%) of 519 isolates in 2004 and 55 (10%) of 548 isolates in 2005 were extended-spectrum beta-lactamase (ESBL) producers with a CTX-M phenotype. Rates of non-beta-lactam resistance and ESBL production were strongly influenced by patient age. The age-stratified rates for dual co-trimoxazole and ciprofloxacin resistance and for ESBL production were 10.9% and 7.6% in women aged 18-35 years, 13% and 6.9% in women aged 36-50 years, 20.4% and 8.8% in women aged 51-64 years, and 23.7% and 11.8% in women aged > or =65 years, respectively. Nitrofurantoin and fosfomycin remain active against >90% of the isolates, irrespective of the resistance phenotypes for other drugs. Our results documented the emergence of problematic resistance phenotypes among community urinary E. coli and highlight the need to explore strategies for their containment.

A case-control study was conducted in order to identify the risk factors associated with bloodstream infection caused by Escherichia coli producing extended-spectrum beta-lactamase (ESBL) and to determine the outcomes of infected patients. Risk factors associated with ESBL production, according to univariate analysis, included a history of recent hospitalization [odds ratio (OR) 4.3, 95% confidence interval (CI) 2.1-8.9; p < 0.001], severe underlying diseases (OR 15, 95% CI 4.4-51.5; p < 0.001), prior exposure to urinary catheters (OR 8.3, 95% CI 3.2-21.7; p < 0.001) and nosocomial (OR 14.1, 95% CI 6.1-32.8; p < 0.001) or urinary (OR 3.6, 95% CI 1.7-7.4; p < 0.001) origin of the bacteria. Multivariate analysis revealed that severe underlying diseases (OR 31.2, 95% CI 6.7-144; p < 0.001) and nosocomial (OR 16.5, 95% CI 5.6-49; p < 0.001) and urinary origins (OR 7.8, 95% CI 2.6-23.8; p < 0.001) of the bacteria were independently associated with ESBL production in bacteremic E. coli. Crude mortality in case patients was more than twice as high as that in controls (p = 0.04). Production of ESBL increased the risk of inappropriate initial therapy (OR 95.6, 95% CI 27.4-334.2; p < 0.001). Treatment failed in 4/7 case patients treated with ceftazidime to which the isolate was susceptible in vitro. Our findings have implications for the choice of empirical therapy in nosocomial urinary tract infection.

The emergence of New Delhi metallo-beta-lactamase (NDM-1) has become a major health threat to clinical managements of gram-negative bacteria infections. A novel incompatibility group X3 plasmid (IncX3) pNDM-HN380 carrying blaNDM-1 has recently been found to epidemiologically link with multiple geographical areas in China. In this paper, we studied the metabolic responses of host bacteria E. coli J53 upon introduction of pNDM-HN380. A reduction of bacterial motility was observed in J53/pNDM-HN380. We profiled the RNA repertoires of the transconjugants and found a downregulation of genes involved in flagella and chemotaxis metabolic pathways at logarithmic (log) phase. We also identified a novel intragenic region (IGR) small RNA plas2. The plasmid-transcribed sRNA IGR plas2 was further characterized as a regulator of fucRwhich controls the fucose metabolism. By knockdown of IGR plas2 using an antisense decoy, we managed to inhibit the formation of bacterial biofilm of the host. Our study demonstrated a potential way of utilizing plasmid-transcribed sRNA against infectious bacteria. [ABSTRACT FROM AUTHOR]

The article discusses the clinical case of a one-year-old infant who was diagnosed with carbapenem-resistant Enterobacteriaceae (CRE). The patient was found to have New Delhi metallo-Β-lactamase (NDM)-1-producing Enterobacteriaceae. The authors concluded that the infant seemed to have acquired the blaNDM-1 gene during hospitalization in Hunan Province, India.