Carriage trends and fitness cost of MDROs in Lebanese nursing homes

Introduction: Nowadays, medical treatments efficiency is challenged by multi drug resistant organisms (MDROs). Lebanese nursing homes’ residents revealed high fecal carriage rates of MDR Enterobacteriacea. Previous studies claim that bacteria with resistant genes experience fitness cost. This study assesses the competitive growth of MDR Escherichia coli and Klebsiella pneumoniae. Methodology: Fecal swabs were collected, during six consecutive months, from ten elderly residing in a Lebanese nursing home. All isolates were subject to API 20E (bioMerieux, Marcy L’ Etoile, France) and antimicrobial susceptibility (Kirby–Bauer method) testing. Phenotypically, ESBL (extended spectrum β-lactamase), MBL (metallo β-lactamase), AmpC and KPC (Klebsiella pneumoniae carbapenemase) were detected using EDTA, PBA, cloxacillin, and DDSTs (Biorad, Hercules, USA). Selected ESBL producing E. coli and K. pneumoniae underwent multiplex PCR analysis. Intra and inter-species in-vitro competition assays were conducted in multiple combinations. Results: Among 117 collected isolates, E. coli was predominant (71.8%); 7.7% were ESBL and 5.1% AmpC producers. With E. coli intra-species assays, sensitive isolates out-competed all others, followed by ESBL, AmpC, and OXA-48 (oxacillin) producers. Inter-species assays, demonstrated a decreased fitness of ESBL producing K. pneumoniae in presence of sensitive E. coli. While out-competing ESBL producing E. coli required 2 sensitive K. pneumoniae isolates. Conclusion: This study highlights resistant E. coli and K. pneumoniae frequency decrease in presence of sensitive isolates, endorsing the fitness cost hypothesis. Hence, competing supplementary species reproducing gut flora, would ensure further steps in the fight against MDROs.

Download Full-text

Zinc limitation in Klebsiella pneumoniae profiled by quantitative proteomics influences transcriptional regulation and cation transporter-associated capsule production

BMC Microbiology ◽

10.1186/s12866-021-02091-8 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

A. Sukumaran ◽

S. Pladwig ◽

J. Geddes-McAlister

Keyword(s):

Klebsiella Pneumoniae ◽

Metal Ion ◽

Ion Homeostasis ◽

Cellular Protein ◽

Pcr Analysis ◽

Phenotypic Analysis ◽

Metal Ion Homeostasis ◽

Capsule Production ◽

The Impact

Abstract Background Microbial organisms encounter a variety of environmental conditions, including changes to metal ion availability. Metal ions play an important role in many biological processes for growth and survival. As such, microbes alter their cellular protein levels and secretion patterns in adaptation to a changing environment. This study focuses on Klebsiella pneumoniae, an opportunistic bacterium responsible for nosocomial infections. By using K. pneumoniae, we aim to determine how a nutrient-limited environment (e.g., zinc depletion) modulates the cellular proteome and secretome of the bacterium. By testing virulence in vitro, we provide novel insight into bacterial responses to limited environments in the presence of the host. Results Analysis of intra- and extracellular changes identified 2380 proteins from the total cellular proteome (cell pellet) and 246 secreted proteins (supernatant). Specifically, HutC, a repressor of the histidine utilization operon, showed significantly increased abundance under zinc-replete conditions, which coincided with an expected reduction in expression of genes within the hut operon from our validating qRT-PCR analysis. Additionally, we characterized a putative cation transport regulator, ChaB that showed significantly higher abundance under zinc-replete vs. -limited conditions, suggesting a role in metal ion homeostasis. Phenotypic analysis of a chaB deletion strain demonstrated a reduction in capsule production, zinc-dependent growth and ion utilization, and reduced virulence when compared to the wild-type strain. Conclusions This is first study to comprehensively profile the impact of zinc availability on the proteome and secretome of K. pneumoniae and uncover a novel connection between zinc transport and capsule production in the bacterial system.

Download Full-text

Meropenem/vaborbactam activity in vitro: a new option for Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae treatment

Future Microbiology ◽

10.2217/fmb-2021-0007 ◽

2021 ◽

Author(s):

Federica Romanelli ◽

Stefania Stolfa ◽

Anna Morea ◽

Luigi Ronga ◽

Raffaele Del Prete ◽

...

Keyword(s):

Klebsiella Pneumoniae ◽

Turning Point ◽

Treatment Strategies ◽

Blood Cultures ◽

Clinical Isolates ◽

In Vitro Susceptibility ◽

Klebsiella Pneumoniae Carbapenemase ◽

Lactamase Inhibitor

Aim: Infections by Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae represent a major challenge because of limited treatment strategies. New β-lactam/β-lactamase inhibitor associations may help to deal with this challenge. The aim of this study is to evaluate the in vitro susceptibility of KPC-producing K. pneumoniae for meropenem/vaborbactam in comparison with ceftazidime/avibactam against. Materials and methods: Twenty-eight strains isolated from blood cultures were evaluated. Testing for susceptibility to meropenem/vaborbactam and ceftazidime/avibactam was performed by E-test gradient strip. Results: All the clinical isolates were susceptible to meropenem/vaborbactam, while one strain was resistant to ceftazidime/avibactam with a MIC of 32 μg/ml. The median MIC of ceftazidime/avibactam evaluated after standardization was higher compared with that of meropenem/vaborbactam. Conclusion: Meropenem/vaborbactam could be an important turning point in the treatment of KPC-producing K. pneumoniae infections, especially considering the emergence of ceftazidime/avibactam resistance.

Download Full-text

In Vitro Activity of a Novel Siderophore-Cephalosporin, GT-1 and Serine-Type β-Lactamase Inhibitor, GT-055, against Escherichia coli, Klebsiella pneumoniae and Acinetobacter spp. Panel Strains

Antibiotics ◽

10.3390/antibiotics9050267 ◽

2020 ◽

Vol 9 (5) ◽

pp. 267 ◽

Cited By ~ 3

Author(s):

Le Phuong Nguyen ◽

Naina Adren Pinto ◽

Thao Nguyen Vu ◽

Hyunsook Lee ◽

Young Lag Cho ◽

...

Keyword(s):

Escherichia Coli ◽

Klebsiella Pneumoniae ◽

Vitro Activity ◽

Intrinsic Activity ◽

In Vitro Activity ◽

E Coli ◽

Acinetobacter Spp ◽

Resistant Strains ◽

Lactamase Inhibitor

This study investigates GT-1 (also known as LCB10-0200), a novel-siderophore cephalosporin, inhibited multidrug-resistant (MDR) Gram-negative pathogen, via a Trojan horse strategy exploiting iron-uptake systems. We investigated GT-1 activity and the role of siderophore uptake systems, and the combination of GT-1 and a non-β-lactam β-lactamase inhibitor (BLI) of diazabicyclooctane, GT-055, (also referred to as LCB18-055) against molecularly characterised resistant Escherichia coli, Klebsiella pneumoniae and Acinetobacter spp. isolates. GT-1 and GT-1/GT-055 were tested in vitro against comparators among three different characterised panel strain sets. Bacterial resistome and siderophore uptake systems were characterised to elucidate the genetic basis for GT-1 minimum inhibitory concentrations (MICs). GT-1 exhibited in vitro activity (≤2 μg/mL MICs) against many MDR isolates, including extended-spectrum β-lactamase (ESBL)- and carbapenemase-producing E. coli and K. pneumoniae and oxacillinase (OXA)-producing Acinetobacter spp. GT-1 also inhibited strains with mutated siderophore transporters and porins. Although BLI GT-055 exhibited intrinsic activity (MIC 2–8 μg/mL) against most E. coli and K. pneumoniae isolates, GT-055 enhanced the activity of GT-1 against many GT-1–resistant strains. Compared with CAZ-AVI, GT-1/GT-055 exhibited lower MICs against E. coli and K. pneumoniae isolates. GT-1 demonstrated potent in vitro activity against clinical panel strains of E. coli, K. pneumoniae and Acinetobacter spp. GT-055 enhanced the in vitro activity of GT-1 against many GT-1–resistant strains.

Download Full-text

Actividad antibacteriana in vitro de aceites esenciales de diferentes especies del género Citrus

Revista Colombiana de Ciencias Químico Farmacéuticas ◽

10.15446/rcciquifa.v46n2.67934 ◽

2017 ◽

Vol 46 (2) ◽

Cited By ~ 2

Author(s):

Miladys Esther Torrenegra Alarcón ◽

Nerlis Paola Pájaro ◽

Glicerio León Méndez

Keyword(s):

Escherichia Coli ◽

Staphylococcus Aureus ◽

Pseudomonas Aeruginosa ◽

Klebsiella Pneumoniae ◽

Staphylococcus Epidermidis ◽

E Coli

Se evaluó la actividad antibacteriana in vitro de aceites esenciales de diferentes especiesdel género Citrus frente a cepas ATCC de Staphylococcus aureus, Staphylococcus epidermidis,Klebsiella pneumoniae, Pseudomonas aeruginosa y Escherichia coli, determinandola concentración mínima inhibitoria (CMI) y la concentración mínima bactericida(CMB). Las bacterias se replicaron en medios de agar y caldos específicos. Se determinóel momento de máxima densidad óptica (DO620) para emplearlo como tiempode incubación; luego se hicieron pruebas de evaluación de sensibilidad con la exposiciónde las cepas a concentraciones a 1000 g/mL del extracto en caldo. Para solubilizarse empleó dimetilsulfóxido (DMSO) al 1%. Posteriormente, se le determinó laconcentración mínima inhibitoria mediante metodologías de microdilución en caldoy la concentración mínima bactericida. Encontrándose una actividad de los aceitesesenciales del género Citrus, con valores de CMI ≥ 600 mg/mL frente a S. aureus,S. epidermidis, K. pneumoniae, P. aeruginosa y E. coli. En función a los resultados obtenidos,se concluye que las diferentes especies del género Citrus son consideradas comopromisorias para el control del componente bacteriano.

Download Full-text

Advantage of the F2:A1:B- IncF Pandemic Plasmid over IncC Plasmids in In Vitro Acquisition and Evolution of blaCTX-M Gene-Bearing Plasmids in Escherichia coli

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01130-19 ◽

2019 ◽

Vol 63 (10) ◽

Cited By ~ 5

Author(s):

Anne-Claire Mahérault ◽

Harry Kemble ◽

Mélanie Magnan ◽

Benoit Gachet ◽

David Roche ◽

...

Keyword(s):

Escherichia Coli ◽

Experimental Evolution ◽

Negative Impact ◽

Fitness Cost ◽

M Gene ◽

Content Type ◽

E Coli ◽

Conjugative Plasmids ◽

K 12

ABSTRACT Despite a fitness cost imposed on bacterial hosts, large conjugative plasmids play a key role in the diffusion of resistance determinants, such as CTX-M extended-spectrum β-lactamases. Among the large conjugative plasmids, IncF plasmids are the most predominant group, and an F2:A1:B- IncF-type plasmid encoding a CTX-M-15 variant was recently described as being strongly associated with the emerging worldwide Escherichia coli sequence type 131 (ST131)-O25b:H4 H30Rx/C2 sublineage. In this context, we investigated the fitness cost of narrow-range F-type plasmids, including the F2:A1:B- IncF-type CTX-M-15 plasmid, and of broad-range C-type plasmids in the K-12-like J53-2 E. coli strain. Although all plasmids imposed a significant fitness cost to the bacterial host immediately after conjugation, we show, using an experimental-evolution approach, that a negative impact on the fitness of the host strain was maintained throughout 1,120 generations with the IncC-IncR plasmid, regardless of the presence or absence of cefotaxime, in contrast to the F2:A1:B- IncF plasmid, whose cost was alleviated. Many chromosomal and plasmid rearrangements were detected after conjugation in transconjugants carrying the IncC plasmids but not in transconjugants carrying the F2:A1:B- IncF plasmid, except for insertion sequence (IS) mobilization from the fliM gene leading to the restoration of motility of the recipient strains. Only a few mutations occurred on the chromosome of each transconjugant throughout the experimental-evolution assay. Our findings indicate that the F2:A1:B- IncF CTX-M-15 plasmid is well adapted to the E. coli strain studied, contrary to the IncC-IncR CTX-M-15 plasmid, and that such plasmid-host adaptation could participate in the evolutionary success of the CTX-M-15-producing pandemic E. coli ST131-O25b:H4 lineage.

Download Full-text

Quercetin Rejuvenates Sensitization of Colistin-Resistant Escherichia coli and Klebsiella Pneumoniae Clinical Isolates to Colistin

Frontiers in Chemistry ◽

10.3389/fchem.2021.795150 ◽

2021 ◽

Vol 9 ◽

Author(s):

Yishuai Lin ◽

Ying Zhang ◽

Shixing Liu ◽

Dandan Ye ◽

Liqiong Chen ◽

...

Keyword(s):

Escherichia Coli ◽

Klebsiella Pneumoniae ◽

Alternative Pathway ◽

Membrane Damage ◽

New Drugs ◽

Colistin Resistance ◽

Cell Membrane Damage ◽

E Coli

Colistin is being considered as “the last ditch” treatment in many infections caused by Gram-negative stains. However, colistin is becoming increasingly invalid in treating patients who are infected with colistin-resistant Escherichia coli (E. coli) and Klebsiella Pneumoniae (K. pneumoniae). To cope with the continuous emergence of colistin resistance, the development of new drugs and therapies is highly imminent. Herein, in this work, we surprisingly found that the combination of quercetin with colistin could efficiently and synergistically eradicate the colistin-resistant E. coli and K. pneumoniae, as confirmed by the synergy checkboard and time-kill assay. Mechanismly, the treatment of quercetin combined with colistin could significantly downregulate the expression of mcr-1 and mgrB that are responsible for colistin-resistance, synergistically enhancing the bacterial cell membrane damage efficacy of colistin. The colistin/quercetin combination was notably efficient in eradicating the colistin-resistant E. coli and K. pneumoniae both in vitro and in vivo. Therefore, our results may provide an efficient alternative pathway against colistin-resistant E. coli and K. pneumoniae infections.

Download Full-text

Aerobactin Seems To Be a Promising Marker Compared With Unstable RmpA2 for the Identification of Hypervirulent Carbapenem-Resistant Klebsiella pneumoniae: In Silico and In Vitro Evidence

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.709681 ◽

2021 ◽

Vol 11 ◽

Author(s):

Chaitra Shankar ◽

Soumya Basu ◽

Binesh Lal ◽

Sathiya Shanmugam ◽

Karthick Vasudevan ◽

...

Keyword(s):

High Risk ◽

Antimicrobial Resistance ◽

Klebsiella Pneumoniae ◽

In Silico ◽

Fitness Cost ◽

Virulence Plasmid ◽

Virulence Determinants ◽

Carbapenem Resistant ◽

Antimicrobial Resistance Genes

BackgroundThe incidence of hypervirulent (hv) carbapenem-resistant (CR) Klebsiella pneumoniae (Kp) is increasing globally among various clones and is also responsible for nosocomial infections. The CR-hvKp is formed by the uptake of a virulence plasmid by endemic high-risk clones or by the uptake of plasmids carrying antimicrobial resistance genes by the virulent clones. Here, we describe CR-hvKp from India belonging to high-risk clones that have acquired a virulence plasmid and are phenotypically unidentified due to lack of hypermucoviscosity.MethodsTwenty-seven CRKp isolates were identified to possess rmpA2 by whole-genome sequencing; and resistance and virulence determinants were characterized. By in silico protein modeling (and validation), protein backbone stability analysis, and coarse dynamics study, the fitness of RmpA, RmpA2, and aerobactin-associated proteins-IucA and IutA, were determined to establish a reliable marker for clinical identification of CR-hvKp.ResultsThe CR-hvKp belonged to multidrug-resistant (MDR) high-risk clones such as CG11, CG43, ST15, and ST231 and carried OXA-232 as the predominant carbapenemase followed by NDM. The virulence plasmid belonged to IncHI1B replicon type and carried frameshifted and truncated rmpA and rmpA2. This resulted in a lack of hypermucoviscous phenotype. However, functional aerobactin was expressed in all high-risk clones. In silico analysis portrayed that IucA and IutA were more stable than classical RmpA. Furthermore, IucA and IutA had lower conformational fluctuations in the functional domains than the non-functional RmpA2, which increases the fitness cost of the latter for its maintenance and expression among CR-hvKp. Hence, RmpA and RmpA2 are likely to be lost among CR-hvKp owing to the increased fitness cost while coding for essential antimicrobial resistance and virulence factors.ConclusionIncreasing incidence of convergence of AMR and virulence is observed among K. pneumoniae globally, which warrants the need for reliable markers for identifying CR-hvKp. The presence of non-functional RmpA2 among high-risk clones highlights the significance of molecular identification of CR-hvKp. The negative string test due to non-functional RmpA2 among CR-hvKp isolates challenges phenotypic screening and faster identification of this pathotype. This can potentially be counteracted by projecting aerobactin as a stable, constitutively expressed, and functional marker for rapidly evolving CR-hvKp.

Download Full-text

Phänotypische Antibiotikaresistenzen von Bakterienisolaten aus Zier-, Zoo- und falknerisch gehaltenen Greifvögeln

Tierärztliche Praxis Ausgabe K Kleintiere / Heimtiere ◽

10.1055/a-1199-6223 ◽

2020 ◽

Vol 48 (04) ◽

pp. 260-269

Author(s):

Leonie Steger ◽

Monika Rinder ◽

Rüdiger Korbel

Keyword(s):

Pseudomonas Aeruginosa ◽

Klebsiella Pneumoniae ◽

Enterococcus Faecalis ◽

Enterobacter Cloacae ◽

Coli Isolate ◽

Aureus Isolate ◽

E Coli ◽

Klinische Relevanz

Zusammenfassung Gegenstand und Ziel Die Prävalenz von antibiotikaresistenten Bakterien bei Zier-, Zoo- und falknerisch gehaltenen Greifvögeln ist noch weitgehend unbekannt. Daher sollten retrospektiv Antibiogramme schnellwachsender aerober Bakterienarten ausgewertet werden. Material und Methoden Im Auswertungszeitraum von 2007 bis 2016 standen 1036 Antibiogramme zur Verfügung. Die Bakterienisolate stammten vorzugsweise aus Süddeutschland und von 811 Vögeln aus 20 zoologischen Ordnungen (am häufigsten Papageienvögel [61,8 %] und Sperlingsvögel [14,5 %]) sowie aus Proben von klinischen Patienten und Sektionsmaterial. Die phänotypische In-vitro-Empfindlichkeit wurde mittels Plattendiffusionstest ermittelt. Ergebnisse Die meisten Antibiogramme lagen für E. coli (n = 386 Isolate) vor, gefolgt von Staphylococcus (S.). aureus (n = 150), Enterobacter cloacae (n = 122), Klebsiella pneumoniae (n = 86) und Pseudomonas aeruginosa (n = 64). Resistenzen gegen mindestens einen antibiotischen Wirkstoff zeigten 53,1 % der E. coli-Isolate, dabei am häufigsten gegen Doxycyclin (50,3 %) und Ampicillin (46,1 %). Bei 78,0 % der S. aureus-Isolate und bei 95,9 % der Enterococcus faecalis-Isolate wurden Resistenzen gegenüber mindestens einem Wirkstoff nachgewiesen. Multiresistenzen (Resistenz gegenüber ≥ 3 Antibiotikagruppen) traten bei 37,3 % der Isolate von S. aureus auf. Bei Isolaten von Zier- und Greifvögeln wurden höhere Resistenzraten festgestellt als bei Isolaten von Zoovögeln und bei Papageienvögeln höhere Resistenzraten als bei Sperlingsvögeln. Im Untersuchungszeitraum zeigte sich bei E. coli ein tendenzieller Anstieg der Resistenzrate für Fluorchinolone (Minimum von 0 % im Jahr 2013 und Maximum von 27,3 % im Jahr 2015) und bei S. aureus eine tendenzielle Abnahme der Resistenzraten für Tetrazykline (Maximum von 39,4 % im Jahr 2007 und Minimum von 0 % in den Jahren 2014 und 2015). Schlussfolgerung und klinische Relevanz Die Resistenzsituation von Bakterien aus Zier-, Zoo- und falknerisch gehaltenen Greifvögeln ist als problematisch zu bewerten und verdeutlicht die Wichtigkeit der Empfindlichkeitsprüfung für eine gewissenhafte Therapie. Im Fall einer Infektion mit S. aureus bei Zier-, Zoo- oder falknerisch gehaltenen Greifvögeln kann es zu einem Therapienotstand kommen.

Download Full-text

In Vitro Activities of the Potent, Broad-Spectrum Carbapenem MK-0826 (L-749,345) against Broad-Spectrum β-Lactamase-and Extended-Spectrum β-Lactamase-Producing Klebsiella pneumoniae and Escherichia coli Clinical Isolates

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.43.5.1170 ◽

1999 ◽

Vol 43 (5) ◽

pp. 1170-1176 ◽

Cited By ~ 51

Author(s):

Joyce Kohler ◽

Karen L. Dorso ◽

Katherine Young ◽

Gail G. Hammond ◽

Hugh Rosen ◽

...

Keyword(s):

Escherichia Coli ◽

Klebsiella Pneumoniae ◽

Broad Spectrum ◽

Bacterial Resistance ◽

Clinical Isolates ◽

Inoculum Level ◽

E Coli ◽

Extended Spectrum ◽

Group 1

ABSTRACT An important mechanism of bacterial resistance to β-lactam antibiotics is inactivation by β-lactam-hydrolyzing enzymes (β-lactamases). The evolution of the extended-spectrum β-lactamases (ESBLs) is associated with extensive use of β-lactam antibiotics, particularly cephalosporins, and is a serious threat to therapeutic efficacy. ESBLs and broad-spectrum β-lactamases (BDSBLs) are plasmid-mediated class A enzymes produced by gram-negative pathogens, principallyEscherichia coli and Klebsiella pneumoniae. MK-0826 was highly potent against all ESBL- and BDSBL-producingK. pneumoniae and E. coli clinical isolates tested (MIC range, 0.008 to 0.12 μg/ml). In E. coli, this activity was associated with high-affinity binding to penicillin-binding proteins 2 and 3. When the inoculum level was increased 10-fold, increasing the amount of β-lactamase present, the MK-0826 MIC range increased to 0.008 to 1 μg/ml. By comparison, similar observations were made with meropenem while imipenem MICs were usually less affected. Not surprisingly, MIC increases with noncarbapenem β-lactams were generally substantially greater, resulting in resistance in many cases. E. coli strains that produce chromosomal (Bush group 1) β-lactamase served as controls. All three carbapenems were subject to an inoculum effect with the majority of the BDSBL- and ESBL-producers but not the Bush group 1 strains, implying some effect of the plasmid-borne enzymes on potency. Importantly, MK-0826 MICs remained at or below 1 μg/ml under all test conditions.

Download Full-text

Fitness cost of mcr-1-mediated polymyxin resistance in Klebsiella pneumoniae

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dky061 ◽

2018 ◽

Vol 73 (6) ◽

pp. 1604-1610 ◽

Cited By ~ 20

Author(s):

Sue C Nang ◽

Faye C Morris ◽

Michael J McDonald ◽

Mei-Ling Han ◽

Jiping Wang ◽

...

Keyword(s):

Klebsiella Pneumoniae ◽

Lipid A ◽

Plasmid Stability ◽

Fitness Cost ◽

Infection Model ◽

Competition Assay ◽

In Vivo Growth ◽

The Impact

Abstract Objectives The discovery of mobile colistin resistance mcr-1, a plasmid-borne polymyxin resistance gene, highlights the potential for widespread resistance to the last-line polymyxins. In the present study, we investigated the impact of mcr-1 acquisition on polymyxin resistance and biological fitness in Klebsiella pneumoniae. Methods K. pneumoniae B5055 was used as the parental strain for the construction of strains carrying vector only (pBBR1MCS-5) and mcr-1 recombinant plasmids (pmcr-1). Plasmid stability was determined by serial passaging for 10 consecutive days in antibiotic-free LB broth, followed by patching on gentamicin-containing and antibiotic-free LB agar plates. Lipid A was analysed using LC–MS. The biological fitness was examined using an in vitro competition assay analysed with flow cytometry. The in vivo fitness cost of mcr-1 was evaluated in a neutropenic mouse thigh infection model. Results Increased polymyxin resistance was observed following acquisition of mcr-1 in K. pneumoniae B5055. The modification of lipid A with phosphoethanolamine following mcr-1 addition was demonstrated by lipid A profiling. The plasmid stability assay revealed the instability of the plasmid after acquiring mcr-1. Reduced in vitro biological fitness and in vivo growth were observed with the mcr-1-carrying K. pneumoniae strain. Conclusions Although mcr-1 confers a moderate level of polymyxin resistance, it is associated with a significant biological fitness cost in K. pneumoniae. This indicates that mcr-1-mediated resistance in K. pneumoniae could be attenuated by limiting the usage of polymyxins.

Download Full-text