Escherichia coli Harboring
 mcr-1
 and
 bla
 CTX-M
 on a Novel IncF Plasmid: First Report of
 mcr-1
 in the United States

McGann, Patrick; Snesrud, Erik; Maybank, Rosslyn; Corey, Brendan W.; Ong, Ana; Clifford, Robert; Hinkle, Mary; Whitman, Timothy J.; Lesho, Emil; Schaecher, Kurt E.

doi:10.1128/aac.01103-16

Cited by 329 publications

(228 citation statements)

References 10 publications

Supporting

Mentioning

214

Contrasting

Unclassified

Order By: Relevance

“…MCR-1 plasmid-1 introduction into Escherichia coli isolates enabling resistance to the last line antibacterial agent colistin, now raises the concern that strains containing both MCR-1 and NDM-1 may emerge that may make routine outpatient urinary tract infections untreatable. 12 And finally, Mycobacterium tuberculosis with the highest global burden of infected individuals of any single pathogen already shows resistance to many classes of antibiotics that make tuberculosis (TB) challenging to treat. 13 …”

Section: Amr Is An Urgent Health Threat and Large Economic Problemmentioning

confidence: 99%

The role of vaccines in fighting antimicrobial resistance (AMR)

Jansen

Anderson

2018

Human Vaccines & Immunotherapeutics

107

View full text Add to dashboard Cite

The problem of antimicrobial resistance (AMR) and the associated morbidity and mortality due to antibiotic resistant bacterial pathogens is not new. However, AMR has been increasing at an alarming rate with appearances of diseases caused by bacteria exhibiting resistance to not just one but multiple classes of antibiotics. The World Health Organization (WHO) supported by governments, health ministries and health agencies has formulated global action plans to combat the rise in AMR, supporting a number of proven initiatives such as antimicrobial stewardship, investments in development of new classes of antibiotics, and educational programs designed to eliminate inappropriate antibiotic use. Vaccines as tools to reduce AMR have historically been under-recognized, yet the positive effect in reducing AMR has been well established. For example Haemophilus influenzae type B (Hib) as well as Streptococcus pneumoniae (pneumococcal) conjugate vaccines have impressive track records in not only preventing life threatening diseases caused by these bacteria, but also reducing antibiotic use and AMR. This paper will describe the drivers of antibiotic use and subsequent development of AMR; it will make the case how existing vaccines are already participating in combatting AMR, describe future prospects for the role of new vaccines in development to reduce AMR, and highlight challenges associated with future vaccine development to combat AMR.

show abstract

Section: Amr Is An Urgent Health Threat and Large Economic Problemmentioning

confidence: 99%

The role of vaccines in fighting antimicrobial resistance (AMR)

Jansen

Anderson

2018

Human Vaccines & Immunotherapeutics

107

View full text Add to dashboard Cite

show abstract

“…In the United States, 11 to 21% and 1 to 6% of UPEC isolates are resistant to trimethoprim-sulfamethoxazole and ciprofloxacin, respectively (9); these drugs are not used when local resistance rates reach 20% and 10%, respectively (8). More troubling is the emergence of multidrug resistance, including resistance to colistin, which is the antibiotic of last resort against Gram-negative bacteria (10). An unabated increase in antibiotic resistance and a lack of new treatments threaten the clinical management of UTI in the future.…”

Section: U Rinary Tract Infection (Uti) Is An Extremely Common Infectmentioning

confidence: 99%

Copper Is a Host Effector Mobilized to Urine during Urinary Tract Infection To Impair Bacterial Colonization

et al. 2017

View full text Add to dashboard Cite

Urinary tract infection (UTI) is a major global infectious disease affecting millions of people annually. Human urinary copper (Cu) content is elevated during UTI caused by uropathogenic Escherichia coli (UPEC). UPEC upregulates the expression of Cu efflux genes during clinical UTI in patients as an adaptive response to host-derived Cu. Whether Cu is mobilized to urine as a host response to UTI and its role in protection against UTI remain unresolved. To address these questions, we tested the hypothesis that Cu is a host effector mobilized to urine during UTI to limit bacterial growth. Our results reveal that Cu is mobilized to urine during UTI caused by the major uropathogens Proteus mirabilis and Klebsiella pneumoniae, in addition to UPEC, in humans. Ceruloplasmin, a Cu-containing ferroxidase, is found at higher levels in UTI urine than in healthy control urine and serves as the molecular source of urinary Cu during UTI. Our results demonstrate that ceruloplasmin decreases the bioavailability of iron in urine by a transferrin-dependent mechanism. Experimental UTI with UPEC in nonhuman primates recapitulates the increased urinary Cu content observed during clinical UTI. Furthermore, Cu-deficient mice are highly colonized by UPEC, indicating that Cu is involved in the limiting of bacterial growth within the urinary tract. Collectively, our results indicate that Cu is a host effector that is involved in protection against pathogen colonization of the urinary tract. Because urinary Cu levels are amenable to modulation, augmentation of the Cu-based host defense against UTI represents a novel approach to limiting bacterial colonization during UTI. KEYWORDS UTI, urinary tract infection, uropathogenic E. coli, UPEC, copper, ceruloplasmin U rinary tract infection (UTI) is an extremely common infectious disease in the UnitedStates and around the world (1, 2). In the United States alone, UTI leads to 11 million physician visits, 1.7 million emergency room visits, and 470,000 hospitalizations annually, with a direct cost of $3.5 billion (2). Infection of the urinary bladder (cystitis) is the most common form of UTI, whereas kidney infection (pyelonephritis), bacteremia, and sepsis are less common but more serious outcomes of UTI (3, 4). Women are four times as likely to develop UTI as men are because of anatomic differences (4). Children, the elderly, and individuals with catheters, anatomic and physiologic abnormalities of the urinary tract, uroliths, or diabetes mellitus are also highly susceptible to UTI (4).Uropathogenic Escherichia coli (UPEC) is the etiological agent in ϳ85% of the cystitis cases in otherwise healthy people (3). Free-living, adherent, biofilm, and intracellular forms of UPEC are found in the urinary bladder (5, 6). UPEC utilizes multiple virulence factors, including type 1 fimbriae, P fimbriae, flagella, toxins, and iron acquisition systems, to cause UTI (2, 7). In addition to UPEC, Klebsiella pneumoniae and Proteus

show abstract

“…Alarmingly, ESBL-encoding IncI2 plasmids are now spreading the colistin resistance determinant mcr-1 in China (101) and Europe (102). The first U.S. case of colistin resistance due to mcr-1 occurred with an E. coli carrying a novel MDR bla CTX-M-55 IncF plasmid earlier this year (103). Although both Salmonella IncI plasmids were cryptic, the ST931R IncI1 plasmid is most similar to pTF2 (KJ563250), a bla CTX-M-1 -encoding plasmid in a Danish E. coli isolate from an unpublished study (99% identity with 89% coverage).…”

Section: Discussionmentioning

confidence: 99%

Whole-Genome Sequencing Identifies In Vivo Acquisition of a bla _CTX-M-27 -Carrying IncFII Transmissible Plasmid as the Cause of Ceftriaxone Treatment Failure for an Invasive Salmonella enterica Serovar Typhimurium Infection

McCollister

Kotter

Frank

et al. 2016

Antimicrob Agents Chemother

View full text Add to dashboard Cite

bWe report a case of ceftriaxone treatment failure for bacteremia caused by Salmonella enterica subsp. enterica serovar Typhimurium, due to the in vivo acquisition of a bla CTX-M-27 -encoding IncFII group transmissible plasmid. The original ␤-lactamasesusceptible isolate ST882S was replaced by the resistant isolate ST931R during ceftriaxone treatment. After relapse, treatment was changed to ciprofloxacin, and the patient recovered. Isolate ST931R could transfer resistance to Escherichia coli at 37°C. We used whole-genome sequencing of ST882S and ST931R, the E. coli transconjugant, and isolated plasmid DNA to unequivocally show that ST882S and ST931R had identical chromosomes, both having 206 identical single-nucleotide polymorphisms (SNPs) versus S. Typhimurium 14028s. We assembled a complete circular genome for ST931R, to which ST882S reads mapped with no SNPs. ST882S and ST931R were isogenic except for the presence of three additional plasmids in ST931R. ST931R and the E. coli transconjugant were ceftriaxone resistant due to the presence of a 60.5-kb IS26-flanked, bla CTX-M-27 -encoding IncFII plasmid. Compared to 14082s, ST931R has almost identical Gifsy-1, Gifsy-2, and ST64B prophages, lacks Gifsy-3, and instead carries a unique Fels-2 prophage related to that found in LT2. ST882S and ST931R both had a 94-kb virulence plasmid showing >99% identity with pSLT14028s and a cryptic 3,904-bp replicon; ST931R also has cryptic 93-kb IncI1 and 62-kb IncI2 group plasmids. To the best of our knowledge, in vivo acquisition of extended-spectrum ␤-lactamase resistance by S. Typhimurium and bla CTX-M-27 genes in U.S. isolates of Salmonella have not previously been reported. G reater than 1.4 million cases of nontyphoidal salmonellosis are estimated to occur each year in the United States, with approximately 95% of cases resulting from foodborne transmission (1). Although most infections result in mild to moderate gastroenteritis that usually resolves with or without treatment, concurrent bacteremia is observed in approximately 6% of patients and can be associated with serious disease, especially in infants aged Ͻ1 year, the elderly, and those with immunocompromised states such as HIV infection (2-5). Although routine use of antimicrobial therapy is not generally recommended for the treatment of most Salmonella infections, such therapy may be lifesaving in persons with invasive disease.Treatment of invasive salmonellosis has been compromised in recent years due to the emergence of Salmonella isolates with single or multidrug resistance to a number of first-line agents (6, 7). Antimicrobial resistance in strains of nontyphoidal Salmonella (NTS) has been linked to the use of antimicrobial agents in livestock (8-11). Consequently, agents such as fluoroquinolones and third generation cephalosporins, such as ceftriaxone, have become treatment modalities of choice for therapy against severe Salmonella infections. In the United States before 1996, all reported cases of infection with ceftriaxone-resistant NTS isolates were known o...

show abstract

Escherichia coli Harboring mcr-1 and bla _CTX-M on a Novel IncF Plasmid: First Report of mcr-1 in the United States

Cited by 329 publications

References 10 publications

The role of vaccines in fighting antimicrobial resistance (AMR)

The role of vaccines in fighting antimicrobial resistance (AMR)

Copper Is a Host Effector Mobilized to Urine during Urinary Tract Infection To Impair Bacterial Colonization

Whole-Genome Sequencing Identifies In Vivo Acquisition of a bla _CTX-M-27 -Carrying IncFII Transmissible Plasmid as the Cause of Ceftriaxone Treatment Failure for an Invasive Salmonella enterica Serovar Typhimurium Infection

Contact Info

Product

Resources

About

Escherichia coli Harboring mcr-1 and bla CTX-M on a Novel IncF Plasmid: First Report of mcr-1 in the United States

Cited by 329 publications

References 10 publications

The role of vaccines in fighting antimicrobial resistance (AMR)

The role of vaccines in fighting antimicrobial resistance (AMR)

Copper Is a Host Effector Mobilized to Urine during Urinary Tract Infection To Impair Bacterial Colonization

Whole-Genome Sequencing Identifies In Vivo Acquisition of a bla CTX-M-27 -Carrying IncFII Transmissible Plasmid as the Cause of Ceftriaxone Treatment Failure for an Invasive Salmonella enterica Serovar Typhimurium Infection

Contact Info

Product

Resources

About

Escherichia coli Harboring mcr-1 and bla _CTX-M on a Novel IncF Plasmid: First Report of mcr-1 in the United States

Whole-Genome Sequencing Identifies In Vivo Acquisition of a bla _CTX-M-27 -Carrying IncFII Transmissible Plasmid as the Cause of Ceftriaxone Treatment Failure for an Invasive Salmonella enterica Serovar Typhimurium Infection