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Fulltext Recombinant Production and Characterization of an Extracellular Subtilisin-Like Serine Protease from Acinetobacter baumannii of Fermented Food Origin

Muhammed NS, Hussin N, Lim AS, Jonet MA, Mohamad SE, Jamaluddin H

Protein J, 2021 06;40(3):419-435.
PMID: 33870461 DOI: 10.1007/s10930-021-09986-5

Acinetobacter baumannii is a ubiquitous bacteria that is increasingly becoming a formidable nosocomial pathogen. Due to its clinical relevance, studies on the bacteria's secretory molecules especially extracellular proteases are of interest primarily in relation to the enzyme's role in virulence. Besides, favorable properties that extracellular proteases possess may be exploited for commercial use thus there is a need to investigate extracellular proteases from Acinetobacter baumannii to gain insights into their catalytic properties. In this study, an extracellular subtilisin-like serine protease from Acinetobacter baumannii designated as SPSFQ that was isolated from fermented food was recombinantly expressed and characterized. The mature catalytically active form of SPSFQ shared a high percentage sequence identity of 99% to extracellular proteases from clinical isolates of Acinetobacter baumannii and Klebsiella pneumoniae as well as a moderately high percentage identity to other bacterial proteases with known keratinolytic and collagenolytic activity. The homology model of mature SPSFQ revealed its structure is composed of 10 β-strands, 8 α-helices, and connecting loops resembling a typical architecture of subtilisin-like α/β motif. SPSFQ is catalytically active at an optimum temperature of 40 °C and pH 9. Its activity is stimulated in the presence of Ca2+ and severely inhibited in the presence of PMSF. SPSFQ also displayed the ability to degrade several tissue-associated protein substrates such as keratin, collagen, and fibrin. Accordingly, our study shed light on the catalytic properties of a previously uncharacterized extracellular serine protease from Acinetobacter baumannii that warrants further investigations into its potential role as a virulence factor in pathogenicity and commercial applications.

Matched MeSH terms: Acinetobacter baumannii/enzymology; Acinetobacter baumannii/genetics*
Fulltext Genomic species identification of Acinetobacter of clinical isolates by 16S rDNA sequencing

Misbah S, Hassan H, Yusof MY, Hanifah YA, AbuBakar S

Singapore Med J, 2005 Sep;46(9):461-4.
PMID: 16123830

This study aims to identify Acinetobacter of clinical isolates from the University of Malaya Medical Centre (UMMC), Kuala Lumpur, to the species level by 16S rDNA sequencing.

Matched MeSH terms: Acinetobacter baumannii/genetics*; Acinetobacter baumannii/isolation & purification
Iron regulated outer membrane proteins (IROMPs) as potential targets against carbapenem-resistant Acinetobacter spp. isolated from a Medical Centre in Malaysia

Hwa WE, Subramaniam G, Mansor MB, Yan OS, Gracie, Anbazhagan D, et al.

Indian J Med Res, 2010 Apr;131:578-83.
PMID: 20424311

Carbapenem-resistant Acinetobacter spp. have gained increasing significance as opportunistic pathogens in hospitalized patients. Carbapenem resistance is often associated with the loss and/or decrease in outer membrane proteins (OMP) and overexpression of multidrug efflux systems. However, carbapenem-hydrolysing beta-lactamases of Ambler Class B (metallo-enzymes) and Ambler Class D (oxacillinases) have also been detected in Acinetobacter spp. In this study we have investigated the role of the iron regulated outer membrane protein (IROMPs) and the loss of a 29-kDa OMP in carbapenem resistance of Acinetobacter calcoaceticus.

Matched MeSH terms: Acinetobacter baumannii/drug effects*; Acinetobacter baumannii/metabolism
Non-polymyxin-based combinations as potential alternatives in treatment against carbapenem-resistant Acinetobacter baumannii infections

Mohd Sazlly Lim S, Naicker S, Ayfan AK, Zowawi H, Roberts JA, Sime FB

Int J Antimicrob Agents, 2020 Oct;56(4):106115.
PMID: 32721600 DOI: 10.1016/j.ijantimicag.2020.106115

Due to limited therapeutic options, combination therapy has been used empirically to treat carbapenem-resistant Acinetobacter baumannii (CRAB). Polymyxin-based combinations have been widely studied and used in the clinical setting. However, the use of polymyxins is often limited due to nephrotoxicity and neurotoxicity. This study aimed to evaluate the activity of non-polymyxin-based combinations relative to polymyxin-based combinations and to identify potential synergistic and bactericidal two-drug non-polymyxin-based combinations against CRAB. In vitro activity of 14 two-drug combinations against 50 A. baumannii isolates was evaluated using the checkerboard method. Subsequently, the two best-performing non-polymyxin-based combinations from the checkerboard assay were explored in static time-kill experiments. Concentrations of antibiotics corresponding to the fractional inhibitory concentrations (FIC) and the highest serum concentration achievable clinically were tested. The most synergistic combinations were fosfomycin/sulbactam (synergistic against 37/50 isolates; 74%), followed by meropenem/sulbactam (synergistic against 28/50 isolates; 56%). No antagonism was observed for any combination. Both fosfomycin/sulbactam and meropenem/sulbactam combinations exhibited bactericidal and synergistic activity against both isolates at the highest clinically achievable concentrations in the time-kill experiments. The meropenem/sulbactam combination displayed synergistic and bactericidal activity against one of two strains at concentrations equal to the FIC. Non-polymyxin-based combinations such as fosfomycin/sulbactam and meropenem/sulbactam may have a role in the treatment of CRAB. Further in vivo and clinical studies are required to scrutinise these activities further.

Matched MeSH terms: Acinetobacter Infections/drug therapy*; Acinetobacter baumannii/drug effects*; Acinetobacter baumannii/isolation & purification
A Systematic Review of the Burden of Multidrug-Resistant Healthcare-Associated Infections Among Intensive Care Unit Patients in Southeast Asia: The Rise of Multidrug-Resistant Acinetobacter baumannii

Teerawattanapong N, Panich P, Kulpokin D, Na Ranong S, Kongpakwattana K, Saksinanon A, et al.

Infect Control Hosp Epidemiol, 2018 05;39(5):525-533.
PMID: 29580299 DOI: 10.1017/ice.2018.58

OBJECTIVETo summarize the clinical burden (cumulative incidence, prevalence, case fatality rate and length of stay) and economic burden (healthcare cost) of healthcare-associated infections (HAIs) due to multidrug-resistant organisms (MDROs) among patients in intensive care units (ICUs) in Southeast Asia.DESIGNSystematic review.METHODSWe conducted a comprehensive literature search in PubMed, EMBASE, CINAHL, EconLit, and the Cochrane Library databases from their inception through September 30, 2016. Clinical and economic burdens and study quality were assessed for each included study.RESULTSIn total, 41 studies met our inclusion criteria; together, 22,876 ICU patients from 7 Southeast Asian countries were included. The cumulative incidence of HAI caused by A. baumannii (AB) in Southeast Asia is substantially higher than has been reported in other regions, especially carbapenem-resistant AB (CRAB; 64.91%) and multidrug-resistant AB (MDR-AB) (58.51%). Evidence of a dose-response relationship between different degrees of drug resistance and excess mortality due to AB infections was observed. Adjusted odds ratios were 1.23 (95% confidence interval [CI], 0.51-3.00) for MDR-AB, 1.72 (95% CI, 0.77-3.80) for extensively drug-resistant AB (XDR-AB), and 1.82 (95% CI, 0.55-6.00) for pandrug-resistant AB (PDR-AB). There is, however, a paucity of published data on additional length of stay and costs attributable to MDROs.CONCLUSIONSThis review highlights the challenges in addressing MDROs in Southeast Asia, where HAIs caused by MDR gram-negative bacteria are abundant and have a strong impact on society. With our findings, we hope to draw the attention of clinicians and policy makers to the problem of antibiotic resistance and to issue a call for action in the management of MDROs.Infect Control Hosp Epidemiol 2018;39:525-533.

Matched MeSH terms: Acinetobacter Infections/drug therapy; Acinetobacter Infections/epidemiology; Acinetobacter baumannii/isolation & purification
Comparative efficacy and safety of treatment options for MDR and XDR Acinetobacter baumannii infections: a systematic review and network meta-analysis

Kengkla K, Kongpakwattana K, Saokaew S, Apisarnthanarak A, Chaiyakunapruk N

J Antimicrob Chemother, 2018 Jan 01;73(1):22-32.
PMID: 29069421 DOI: 10.1093/jac/dkx368

Objectives: To comprehensively compare and rank the efficacy and safety of available treatment options for patients with MDR and XDR Acinetobacter baumannii (AB) infection.
Methods: We searched PubMed, Embase and the Cochrane register of trials systematically for studies that examined treatment options for patients with MDR- and XDR-AB infections until April 2016. Network meta-analysis (NMA) was performed to estimate the risk ratio (RR) and 95% CI from both direct and indirect evidence. Primary outcomes were clinical cure and microbiological cure. Secondary outcomes were all-cause mortality and nephrotoxic and non-nephrotoxic adverse events.
Results: A total of 29 studies with 2529 patients (median age 60 years; 65% male; median APACHE II score 19.0) were included. Although there were no statistically significant differences between treatment options, triple therapy with colistin, sulbactam and tigecycline had the highest clinical cure rate. Colistin in combination with sulbactam was associated with a significantly higher microbiological cure rate compared with colistin in combination with tigecycline (RR 1.23; 95% CI 1.03-1.47) and colistin monotherapy (RR 1.21; 95% CI 1.06-1.38). No significant differences in all-cause mortality were noted between treatment options. Tigecycline-based therapy also appeared less effective for achieving a microbiological cure and is not appropriate for treating bloodstream MDR- and XDR-AB infections.
Conclusions: Combination therapy of colistin with sulbactam demonstrates superiority in terms of microbiological cure with a safety profile similar to that of colistin monotherapy. Thus, our findings support the use of this combination as a treatment for MDR- and XDR-AB infections.

Matched MeSH terms: Acinetobacter Infections/drug therapy*; Acinetobacter Infections/microbiology; Acinetobacter baumannii/drug effects*
Fulltext Risk factors and outcomes of imipenem-resistant Acinetobacter bloodstream infection in North-Eastern Malaysia

Deris ZZ, Shafei MN, Harun A

Asian Pac J Trop Biomed, 2011 Aug;1(4):313-5.
PMID: 23569782 DOI: 10.1016/S2221-1691(11)60050-6

To determine the risk factors and outcomes of imipenem-resistant Acinetobacter baumannii (IRAB) bloodstream infection (BSI) cases, since there is very little publication on Acinetobacter baumannii infections from Malaysia.

Matched MeSH terms: Acinetobacter Infections/drug therapy*; Acinetobacter Infections/microbiology; Acinetobacter Infections/epidemiology; Acinetobacter baumannii/drug effects*; Acinetobacter baumannii/isolation & purification
Outcomes and appropriateness of management of nosocomial Acinetobacter bloodstream infections at a teaching hospital in northeastern Malaysia

Deris ZZ, Harun A, Shafei MN, Rahman RA, Johari MR

Southeast Asian J. Trop. Med. Public Health, 2009 Jan;40(1):140-7.
PMID: 19323046

Acinetobacter spp is a known nosocomial pathogen causing a wide range of clinical diseases such as pneumonia, wound infection and bloodstream infections (BSI). The clinical outcomes of acinetobacter BSI were determined by a 1:1 case control study involving 58 confirmed cases of acinetobacter BSI who were compared to other gram-negative infections. The crude mortality of acinetobacter BSI was 47.2%, which was significantly greater than other gram-negative BSI (OR 1.89, 95% CI 1.10-3.24) but there were no significant differences in attributed mortality between the two groups. We found that patients treated in intensive care units (ICU), who had longer ICU stays, who presented with shock or coagulopathy, had prior exposure to carbapenems, had mechanical ventilation, were on a ventilator for longer periods, had a nasogastric tube, had an arterial catheter or had parenteral nutrition at a significantly greater risk of mortality due to acinetobacter BSI. Patients presenting with septic shock (OR 17.95, 95% CI 3.36-95.84) or having a central venous catheter (OR 12.48, 95% CI 1.09-142.68) were independently at higher risk for mortality. Appropriateness of therapy reduced the mortality attributes of acinetobacter BSI (OR 0.197, 95% CI 0.040-0.967) but did not significantly reduce crude mortality in acinetobacter BSI patients. This study shows the importance of preventing acinetobacter BSI and the appropriate use of antimicrobial agents to reduce mortality.

Matched MeSH terms: Acinetobacter/drug effects*; Acinetobacter/isolation & purification; Acinetobacter Infections/drug therapy*; Acinetobacter Infections/microbiology; Acinetobacter Infections/mortality*
Molecular characterization of carbapenemase and cephalosporinase genes among clinical isolates of Acinetobacter baumannii in a tertiary medical centre in Malaysia

Biglari S, Alfizah H, Ramliza R, Rahman MM

J Med Microbiol, 2015 Jan;64(Pt 1):53-8.
PMID: 25381148 DOI: 10.1099/jmm.0.082263-0

Antimicrobial resistance in Acinetobacter baumannii is a growing public health concern and an important pathogen in nosocomial infections. We investigated the genes involved in resistance to carbapenems and cephalosporins in clinical A. baumannii isolates from a tertiary medical centre in Malaysia. A. baumannii was isolated from 167 clinical specimens and identified by sequencing of the 16S rRNA and rpoB genes. The MIC for imipenem, meropenem, ceftazidime and cefepime were determined by the E-test method. The presence of carbapenemase and cephalosporinase genes was investigated by PCR. The isolates were predominantly nonsusceptible to carbapenems and cephalosporins (>70 %) with high MIC values. ISAba1 was detected in all carbapenem-nonsusceptible A. baumannii harbouring the blaOXA-23-like gene. The presence of blaOXA-51-like and ISAba1 upstream of blaOXA-51 was not associated with nonsusceptibility to carbapenems. A. baumannii isolates harbouring ISAba1-blaADC (85.8 %) were significantly associated with nonsusceptibility to cephalosporins (P<0.0001). However, ISAba1-blaADC was not detected in a minority (<10 %) of the isolates which were nonsusceptible to cephalosporins. The acquired OXA-23 enzymes were responsible for nonsusceptibility to carbapenems in our clinical A. baumannii isolates and warrant continuous surveillance to prevent further dissemination of this antibiotic resistance gene. The presence of ISAba1 upstream of the blaADC was a determinant for cephalosporin resistance. However, the absence of this ISAba1-blaADC in some of the isolates may suggest other resistance mechanisms and need further investigation.

Matched MeSH terms: Acinetobacter Infections/microbiology*; Acinetobacter baumannii/enzymology*; Acinetobacter baumannii/genetics; Acinetobacter baumannii/isolation & purification
Isotherm kinetics of Cr(III) removal by non-viable cells of Acinetobacter haemolyticus

Yahya SK, Zakaria ZA, Samin J, Raj AS, Ahmad WA

Colloids Surf B Biointerfaces, 2012 Jun 1;94:362-8.
PMID: 22398363 DOI: 10.1016/j.colsurfb.2012.02.016

The potential use of non-viable biomass of a Gram negative bacterium i.e. Acinetobacter haemolyticus to remove Cr(III) species from aqueous environment was investigated. Highest Cr(III) removal of 198.80 mg g(-1) was obtained at pH 5, biomass dosage of 15 mg cell dry weight, initial Cr(III) of 100 mg L(-1) and 30 min of contact time. The Langmuir and Freundlich models fit the experimental data (R(2)>0.95) while the kinetic data was best described using the pseudo second-order kinetic model (R(2)>0.99). Cr(III) was successfully recovered from the bacterial biomass using either 1M of CH(3)COOH, HNO(3) or H(2)SO(4) with 90% recovery. TEM and FTIR suggested the involvement of amine, carboxyl, hydroxyl and phosphate groups during the biosorption of Cr(III) onto the cell surface of A. haemolyticus. A. haemolyticus was also capable to remove 79.87 mg g(-1) Cr(III) (around 22.75%) from raw leather tanning wastewater. This study demonstrates the potential of using A. haemolyticus as biosorbent to remove Cr(III) from both synthetic and industrial wastewater.

Matched MeSH terms: Acinetobacter/ultrastructure; Acinetobacter/chemistry*
In silico and empirical approaches toward understanding the structural adaptation of the alkaline-stable lipase KV1 from Acinetobacter haemolyticus

Batumalaie K, Edbeib MF, Mahat NA, Huyop F, Wahab RA

J Biomol Struct Dyn, 2018 Sep;36(12):3077-3093.
PMID: 28884626 DOI: 10.1080/07391102.2017.1377635

Interests in Acinetobacter haemolyticus lipases are showing an increasing trend concomitant with growth of the enzyme industry and the widening search for novel enzymes and applications. Here, we present a structural model that reveals the key catalytic residues of lipase KV1 from A. haemolyticus. Homology modeling of the lipase structure was based on the structure of a carboxylesterase from the archaeon Archaeoglobus fulgidus as the template, which has a sequence that is 58% identical to that of lipase KV1. The lipase KV1 model is comprised of a single compact domain consisting of seven parallel and one anti-parallel β-strand surrounded by nine α-helices. Three structurally conserved active-site residues, Ser165, Asp259, and His289, and a tunnel through which substrates access the binding site were identified. Docking of the substrates tributyrin and palmitic acid into the pH 8 modeled lipase KV1 active sites revealed an aromatic platform responsible for the substrate recognition and preference toward tributyrin. The resulting binding modes from the docking simulation correlated well with the experimentally determined hydrolysis pattern, for which pH 8 and tributyrin being the optimum pH and preferred substrate. The results reported herein provide useful insights into future structure-based tailoring of lipase KV1 to modulate its catalytic activity.

Matched MeSH terms: Acinetobacter/enzymology; Acinetobacter/chemistry*
Fulltext Risk factors associated with multi-drug-resistant Acinetobacter baumannii nosocomial infections at a tertiary care hospital in Makkah, Saudi Arabia - a matched case-control study

Al-Gethamy MM, Faidah HS, Adetunji HA, Haseeb A, Ashgar SS, Mohanned TK, et al.

J Int Med Res, 2017 Jun;45(3):1181-1189.
PMID: 28480813 DOI: 10.1177/0300060517706284

Objective To determine risk factors for multi-drug-resistant Acinetobacter baumannii (MDR-AB) nosocomial infections in intensive care units in a tertiary care hospital, Makkah, Saudi Arabia. Methods We performed a hospital-based, matched case-control study in patients who were admitted to Al Noor Specialist Hospital between 1 January 2012 and 31 August 2012. The study included cases of A. baumannii nosocomial infection and controls without infection. Controls were matched to cases by age and ward of admission. Results The most frequent site of infection was the respiratory tract (77.3%). Susceptibility to antimicrobial MDR-AB was 92.0% for ceftazidime and ciprofloxacin, while it was 83.3% for imipenem, 83.0% for trimethoprim, 79.0% for amikacin, and 72.7% for gentamicin. Multiple logistic regression of risk factors showed that immunosuppression (OR = 2.9; 95% CI 1.5-5.6; p = 0.002), clinical outcome (OR = 0.4; 95% CI 0.3-0.9; p = 0.01), invasive procedures (OR = 7.9; 95% CI 1.8-34.2; p = 0.002), a central venous catheter (OR = 2.9; 95% CI 1.5-5.6; p = 0.000), and an endotracheal tube (OR = 3.4; 95% CI 1.6-7.3; p = 0.001) were associated with MDR-AB. Conclusions Acinetobacter nosocomial infections are associated with admission to the ICU (Intensive care unit) and exposure to invasive procedures.

Matched MeSH terms: Acinetobacter baumannii/drug effects*; Acinetobacter baumannii/isolation & purification
In silico mutation on a mutant lipase from Acinetobacter haemolyticus towards enhancing alkaline stability

Anuar NFSK, Wahab RA, Huyop F, Halim KBA, Hamid AAA

J Biomol Struct Dyn, 2020 Sep;38(15):4493-4507.
PMID: 31630644 DOI: 10.1080/07391102.2019.1683074

Alkaline-stable lipases are highly valuable biocatalysts that catalyze reactions under highly basic conditions. Herein, computational predictions of lipase from Acinetobacter haemolyticus and its mutant, Mut-LipKV1 was performed to identify functionally relevant mutations that enhance pH performance under increasing basicity. Mut-LipKV1 was constructed by in silico site directed mutagenesis of several outer loop acidic residues, aspartic acid (Asp) into basic ones, lysine (Lys) at positions 51, 122 and 247, followed by simulation under extreme pH conditions (pH 8.0-pH 12.0). The energy minimized Mut-LipKV1 model exhibited good quality as shown by PROCHECK, ERRAT and Verify3D data that corresponded to 79.2, 88.82 and 89.42% in comparison to 75.2, 86.15, and 95.19% in the wild-type. Electrostatic surface potentials and charge distributions of the Mut-LipKV1 model was more stable and better adapted to conditions of elevated pHs (pH 8.0 - 10.0). Mut-LipKV1 exhibited a mixture of neutral and positive surface charge distribution compared to the predominantly negative charge in the wild-type lipase at pH 8.0. Data of molecular dynamics simulations also supported the increased alkaline-stability of Mut-LipKV1, wherein the lipase was more stable at a higher pH 9.0 (RMSD = ∼0.3 nm, RMSF = ∼0.05-0.2 nm), over the optimal pH 8.0 of the wild-type lipase (RMSD = 0.3 nm, RMSF = 0.05-0.20 nm). Thus, the adaptive strategy of replacing surface aspartic acid to lysine in lipase was successful in yielding a more alkaline-stable Mut-LipKV1 under elevated basic conditions.Communicated by Ramaswamy H. Sarma.

Matched MeSH terms: Acinetobacter
Maternal and neonatal effects of Acinetobacter colonisation in preterm premature rupture of membrane and term labour

Sood M, Mohd Zain Z, Abu NA, Chee SC, Mohd Nor NS

Med J Malaysia, 2019 02;74(1):40-44.
PMID: 30846661

INTRODUCTION: Some anecdotal reports suggest that maternal colonisation with Acinetobacter baumannii during pregnancy is associated with adverse maternal and neonatal effects, including preterm premature rupture of membrane (PPROM). The objective of this study was to compare the maternal and neonatal effects of A. baumannii colonisation in cases with PPROM and those with spontaneous onset of labour at term.
METHODS: The recruitment of participants' was carried out at Selayang Hospital, Selangor, Malaysia. Vaginal swabs were prospectively taken from 104 patients of PPROM and 111 with spontaneous onset of labour at term. Swabs were also taken from the axillae and ears of their babies. These swabs were cultured to isolate A. baumannii. Maternal and neonatal adverse outcomes were documented.
RESULTS: Sixteen mothers were A. baumannii positive, eight from each group respectively. None of the cases developed chorioamnionitis or sepsis. Those positive were four cases of PPROM and two babies of term labour. None of the babies developed sepsis.
CONCLUSIONS: This study does not support the suggestion that A. baumannii colonisation during pregnancy is associated with adverse maternal and neonatal outcomes.

Matched MeSH terms: Acinetobacter Infections/complications*; Acinetobacter baumannii*
Multidrug-resistant Acinetobacter baumannii infections: Current evidence on treatment options and the role of pharmacokinetics/pharmacodynamics in dose optimisation

Mohd Sazlly Lim S, Sime FB, Roberts JA

Int J Antimicrob Agents, 2019 Jun;53(6):726-745.
PMID: 30831234 DOI: 10.1016/j.ijantimicag.2019.02.016

Acinetobacter baumannii remains a difficult-to-treat pathogen that poses a significant challenge to clinicians and costs to the healthcare system. There is a lack of clinical efficacy data to aid in the selection of optimal treatment for multidrug-resistant (MDR) A. baumannii infections. This paper aimed to review recent literature on the treatment of MDR A. baumannii infections and novel agents in the pipeline and to discuss the clinical data supporting their use. Colistin has been widely studied as monotherapy or as part of combination therapy, but its use is limited due to nephrotoxicity. The clinical benefit of combination therapy, whether empirical or targeted, has yet to be demonstrated owing to a lack of definitive evidence from randomised controlled trials (RCTs). Most available clinical studies are retrospective and lack control groups, which offers low-grade evidence. Novel agents such as cefiderocol, plazomicin, eravacycline and sulbactam/ETX2514 combination are promising options for the treatment of different infectious pathologies caused by MDR A. baumannii, but these have yet to be evaluated in RCTs. A better understanding of the pharmacokinetics/pharmacodynamics of the 'old' antibiotics is required to optimise their dosing regimens in order to maximise bacterial killing, minimise toxicities and improve clinical outcomes.

Matched MeSH terms: Acinetobacter baumannii
Fulltext Imipenem Treatment Induces Expression of Important Genes and Phenotypes in a Resistant Acinetobacter baumannii Isolate

Dhabaan GN, AbuBakar S, Cerqueira GM, Al-Haroni M, Pang SP, Hassan H

Antimicrob Agents Chemother, 2015 Dec 14;60(3):1370-6.
PMID: 26666943 DOI: 10.1128/AAC.01696-15

Acinetobacter baumannii has emerged as a notorious multidrug-resistant pathogen, and development of novel control measures is of the utmost importance. Understanding the factors that play a role in drug resistance may contribute to the identification of novel therapeutic targets. Pili are essential for A. baumannii adherence to and biofilm formation on abiotic surfaces as well as virulence. In the present study, we found that biofilm formation was significantly induced in an imipenem-resistant (Imp(r)) strain treated with a subinhibitory concentration of antibiotic compared to that in an untreated control and an imipenem-susceptible (Imp(s)) isolate. Using microarray and quantitative PCR analyses, we observed that several genes responsible for the synthesis of type IV pili were significantly upregulated in the Imp(r) but not in the Imp(s) isolate. Notably, this finding is corroborated by an increase in the motility of the Imp(r) strain. Our results suggest that the ability to overproduce colonization factors in response to imipenem treatment confers biological advantage to A. baumannii and may contribute to clinical success.

Matched MeSH terms: Acinetobacter baumannii/drug effects*; Acinetobacter baumannii/genetics*; Acinetobacter baumannii/physiology
Fulltext The prevalence and risk factors of nosocomial Acinetobacter blood stream infections in tertiary teaching hospital in north-eastern Malaysia

Deris ZZ, Harun A, Omar M, Johari MR

Trop Biomed, 2009 Aug;26(2):123-9, 219-22.
PMID: 19901898

Acinetobacter spp. is a known nosocomial pathogen causing a wide range of clinical diseases mainly pneumonia, wound infections and blood stream infections (BSI). A cross sectional descriptive study was performed to determine the prevalence of Acinetobacter infection in Hospital Universiti Sains Malaysia, Kelantan (HUSM). The risk factors of Acinetobacter BSI were determined by 1:1 case control analytical study, involving fifty-eight confirmed cases of Acinetobacter BSI patients compared to the cases caused by Gram-negative bacteria. The prevalence of Acinetobacter BSI in the HUSM was 6.11% (95% CI 4.88-7.53%). The attack rate of Acinetobacter BSI was 2.77 episodes per 1000 hospital admissions. Acinetobacter BSI patients were mostly located in intensive care unit and had a longer intensive care unit stay. In univariate analysis, the risk factors for Acinetobacter BSI include prior exposure to antimicrobial agents such as penicillins, aminoglycosides and cephalosporins, mechanical ventilation, presence of nasogastric tube, arterial catheter and urinary catheter. In multivariate analysis, the independent risk factors for Acinetobacter BSI were prior treatment with cephalosporins (OR 3.836 95% CI 1.657-8.881 p=0.002) and mechanical ventilation (OR 3.164 95% CI 1.353-7.397 p=0.008). This study revealed that rational use of antimicrobial agents is of paramount importance to control Acinetobacter BSI.

Matched MeSH terms: Acinetobacter Infections/drug therapy; Acinetobacter Infections/microbiology; Acinetobacter Infections/epidemiology*
Fulltext Structure-Based Screening of Non-β-Lactam Inhibitors against Class D β-Lactamases: An Approach of Docking and Molecular Dynamics

Gupta D, Singh A, Somvanshi P, Singh A, Khan AU

ACS Omega, 2020 Apr 28;5(16):9356-9365.
PMID: 32363287 DOI: 10.1021/acsomega.0c00356

The manifestation of class D β-lactamases in the community raises significant concern as they can hydrolyze carbapenem antibiotics. Hence, it is exceptionally alluring to design novel inhibitors. Structure-based virtual screening using docking programs and molecular dynamics simulations was employed to identify two novel non-β-lactam compounds that possess the ability to block different OXA variants. Furthermore, the presence of a nonpolar aliphatic amino acid, valine, near the active site serine, was identified in all OXA variants that can be accounted to block the catalytic activity of OXA enzymes.

Matched MeSH terms: Acinetobacter baumannii
Fulltext Characterization of affinity-purified isoforms of Acinetobacter calcoaceticus Y1 glutathione transferases

Chee CS, Tan IK, Alias Z

ScientificWorldJournal, 2014;2014:750317.
PMID: 24892084 DOI: 10.1155/2014/750317

Glutathione transferases (GST) were purified from locally isolated bacteria, Acinetobacter calcoaceticus Y1, by glutathione-affinity chromatography and anion exchange, and their substrate specificities were investigated. SDS-polyacrylamide gel electrophoresis revealed that the purified GST resolved into a single band with a molecular weight (MW) of 23 kDa. 2-dimensional (2-D) gel electrophoresis showed the presence of two isoforms, GST1 (pI 4.5) and GST2 (pI 6.2) with identical MW. GST1 was reactive towards ethacrynic acid, hydrogen peroxide, 1-chloro-2,4-dinitrobenzene, and trans,trans-hepta-2,4-dienal while GST2 was active towards all substrates except hydrogen peroxide. This demonstrated that GST1 possessed peroxidase activity which was absent in GST2. This study also showed that only GST2 was able to conjugate GSH to isoproturon, a herbicide. GST1 and GST2 were suggested to be similar to F0KLY9 (putative glutathione S-transferase) and F0KKB0 (glutathione S-transferase III) of Acinetobacter calcoaceticus strain PHEA-2, respectively.

Matched MeSH terms: Acinetobacter calcoaceticus/enzymology*
Bacterial reduction of Cr(VI) at technical scale--the Malaysian experience

Zakaria ZA, Ahmad WA, Zakaria Z, Razali F, Karim NA, Sum MM, et al.

Appl Biochem Biotechnol, 2012 Jul;167(6):1641-52.
PMID: 22350941 DOI: 10.1007/s12010-012-9608-9

The bacterial reduction of Cr(VI) from industrial wastewater was evaluated using a 2.0-m(3) bioreactor. Liquid pineapple waste was used as a nutrient for the biofilm community formed inside the bioreactor. The use of rubber wood sawdust as packing material was able to immobilize more than 10(6) CFU mL(-1) of Acinetobacter haemolyticus cells after 3 days of contact time. Complete reduction of 15-240 mg L(-1) of Cr(VI) was achieved even after 3 months of bioreactor operation. Cr(VI) was not detected in the final effluent fraction indicating complete removal of Cr from solution from the flocculation/coagulation step and the unlikely re-oxidation of Cr(III) into Cr(VI). Impatiens balsamina L. and Gomphrena globosa L. showed better growth in the presence of soil-sludge mixture compared to Coleus scutellarioides (L.) Benth. Significant amounts of Cr accumulated at different sections of the plants indicate its potential application in Cr phytoremediation effort. The bacterial-based system was also determined not to be detrimental to human health based on the low levels of Cr detected in the hair and nail samples of the plant operators. Thus, it can be said that bacterial-based Cr(VI) treatment system is a feasible alternative to the conventional system especially for lower Cr(VI) concentrations, where sludge generated can be used as growth supplement for ornamental plant as well as not detrimental to the health of the workers.

Matched MeSH terms: Acinetobacter/metabolism*

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