Analysis of Antimicrobial and Antibiofilm Activity of Human Milk Lactoferrin Compared to Bovine Lactoferrin against Multidrug Resistant and Susceptible <i>Acinetobacter baumannii</i> Clinical Isolates

Avery, Tyra M; Boone, Ranashia L.; Lu, Jacky; Spicer, Sabrina K.; Guevara, Miriam A.; Moore, Rebecca E.; Chambers, Schuyler A.; Manning, Shannon D.; Dent, Leon; Marshall, Dana; Damo, Steven M.; Townsend, Steven D.; Gaddy, Jennifer A.

doi:10.1021/acsinfecdis.1c00087

Cited by 25 publications

(14 citation statements)

References 44 publications

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“…Lactoferrin's binding affinity for iron is 300 times higher than that of transferrin. These observations provide evidence that indicates the complex interplay between this pathogen's and both human and bovine isoforms of host products [42]. Together, these observations demonstrate how human proteins can have an important and significant impact on biofilm formation.…”

Section: Hsa and Hs Negatively Affects Biofilm Formationmentioning

confidence: 58%

“…Another human molecule that also exhibited biofilm formation inhibition in A. baumannii strains was L-Adrenaline [41]. In addition, a recent study reported that lactoferrin has antimicrobial and antibiofilm activities against A. baumannii clinical strains that were isolated from wounds, blood, urine, and sputum/bronchial wash [42]. Lactoferrin is an innate immune glycoprotein produced in high concentrations in both human and bovine milk, and is considered one of the most effective iron chelators.…”

Section: Quorum Network Is Altered By Hsa and Hsmentioning

confidence: 99%

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Interaction of Acinetobacter baumannii with Human Serum Albumin: Does the Host Determine the Outcome?

Pimentel

Tuttobene

et al. 2021

Antibiotics

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Acinetobacter baumannii has become a serious threat to human health due to its extreme antibiotic resistance, environmental persistence, and capacity to survive within the host. Two A. baumannii strains, A118 and AB5075, commonly used as model systems, and three carbapenem-resistant strains, which are becoming ever more dangerous due to the multiple drugs they can resist, were exposed to 3.5% human serum albumin (HSA) and human serum (HS) to evaluate their response with respect to antimicrobial resistance, biofilm formation, and quorum sensing, all features responsible for increasing survival and persistence in the environment and human body. Expression levels of antibiotic resistance genes were modified differently when examined in different strains. The cmlA gene was upregulated or downregulated in conditions of exposure to 3.5% HSA or HS depending on the strain. Expression levels of pbp1 and pbp3 tended to be increased by the presence of HSA and HS, but the effect was not seen in all strains. A. baumannii A118 growing in the presence of HS did not experience increased expression of these genes. Aminoglycoside-modifying enzymes were also expressed at higher or lower levels in the presence of HSA or HS. Still, the response was not uniform; in some cases, expression was enhanced, and in other cases, it was tapered. While A. baumannii AB5075 became more susceptible to rifampicin in the presence of 3.5% HSA or HS, strain A118 did not show any changes. Expression of arr2, a gene involved in resistance to rifampicin present in A. baumannii AMA16, was expressed at higher levels when HS was present in the culture medium. HSA and HS reduced biofilm formation and production of N-Acyl Homoserine Lactone, a compound intimately associated with quorum sensing. In conclusion, HSA, the main component of HS, stimulates a variety of adaptative responses in infecting A. baumannii strains.

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Section: Hsa and Hs Negatively Affects Biofilm Formationmentioning

confidence: 58%

Section: Quorum Network Is Altered By Hsa and Hsmentioning

confidence: 99%

Interaction of Acinetobacter baumannii with Human Serum Albumin: Does the Host Determine the Outcome?

Pimentel

Tuttobene

et al. 2021

Antibiotics

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“…The utility of human milk as a prebiotic that can protect against a variety of infections has been well demonstrated in the literature. ,, Infants whose primary source of nutrition, which is derived from human breast milk, have enhanced protection against diarrhea, respiratory infection, urinary tract infection, ear infection, necrotizing enterocolitis (NEC), and specifically, infection with Escherichia coli , Clostridioides difficile , and Campylobacter jejuni . − Human milk harbors a variety of antimicrobial molecules that can inhibit the growth and viability of a variety of pathogenic microbes as well as immune-modulating molecules that influence inflammation responses to invading pathogens . Our recent work and the work of others has demonstrated that the human milk glycoprotein lactoferrin has antimicrobial and antibiofilm activities against A. baumannii and other bacteria, including S. agalactiae , S. aureus , and Pseudomonas aeruginosa . − In addition to the proteinaceous components of milk, the human milk glycome is also of particular interest, as components within this population of molecules have been associated with strong protection against infection by enteric pathogens …”

Section: Discussionmentioning

confidence: 99%

Antibiofilm Activity of Human Milk Oligosaccharides against Multidrug Resistant and Susceptible Isolates of Acinetobacter baumannii

Spicer

Moore

et al. 2021

ACS Infect. Dis.

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Acinetobacter baumannii is a serious threat to human health, per the Centers for Disease Control and Prevention's latest threat assessment. A. baumannii is a Gram-negative opportunistic bacterial pathogen that causes severe community and nosocomial infections in immunocompromised patients. Treatment of these infections is confounded by the emergence of multi-and pan-drug resistant strains of A. baumannii. A. baumannii colonizes abiotic and biotic surfaces and evades antimicrobial challenges by forming biofilms, which are three-dimensional architectural structures of cells adhered to a substrate and encased in an extracellular matrix comprised of polymeric substances such as polysaccharides, proteins, and DNA. Biofilm-inhibiting compounds have recently gained attention as a chemotherapeutic strategy to prevent or disperse A. baumannii biofilms and restore the utility of traditional antimicrobial strategies. Recent work indicates that human milk oligosaccharides (HMOs) have potent antibacterial and biofilm-inhibiting properties. We sought to test the utility of HMOs against a bank of clinical isolates of A. baumannii to ascertain changes in bacterial growth or biofilm formation. Our results indicate that out of 18 strains tested, 14 were susceptible to the antibiofilm activities of HMOs, and that the potent antibiofilm activity was observed in strains isolated from diverse anatomical sites, disease manifestations, and across antibioticresistant and susceptible strains.

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“…Human AMP LL37 is one such AMP that inhibits A. baumannii biofilm ( 291 ). Human milk lactoferrin which is an iron-chelating AMP also showed slightly more potent antibacterial activity than bovine milk lactoferrin against A. baumannii biofilm ( 292 ). Derivative (D-RR4) of a small synthetic peptide, RR (12 amino acids) exhibited potent antibacterial and anti-biofilm activity against P. aeruginosa and A. baumannii in macrophage cells as well as in a Caenorhabditis elegans model ( 293 ).…”

Section: Strategies Of Preventing a Baumannii Biof...mentioning

confidence: 99%

Convergence of Biofilm Formation and Antibiotic Resistance in Acinetobacter baumannii Infection

et al. 2022

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Acinetobacter baumannii (A. baumannii) is a leading cause of nosocomial infections as this pathogen has certain attributes that facilitate the subversion of natural defenses of the human body. A. baumannii acquires antibiotic resistance determinants easily and can thrive on both biotic and abiotic surfaces. Different resistance mechanisms or determinants, both transmissible and non-transmissible, have aided in this victory over antibiotics. In addition, the propensity to form biofilms (communities of organism attached to a surface) allows the organism to persist in hospitals on various medical surfaces (cardiac valves, artificial joints, catheters, endotracheal tubes, and ventilators) and also evade antibiotics simply by shielding the bacteria and increasing its ability to acquire foreign genetic material through lateral gene transfer. The biofilm formation rate in A. baumannii is higher than in other species. Recent research has shown how A. baumannii biofilm-forming capacity exerts its effect on resistance phenotypes, development of resistome, and dissemination of resistance genes within biofilms by conjugation or transformation, thereby making biofilm a hotspot for genetic exchange. Various genes control the formation of A. baumannii biofilms and a beneficial relationship between biofilm formation and “antimicrobial resistance” (AMR) exists in the organism. This review discusses these various attributes of the organism that act independently or synergistically to cause hospital infections. Evolution of AMR in A. baumannii, resistance mechanisms including both transmissible (hydrolyzing enzymes) and non-transmissible (efflux pumps and chromosomal mutations) are presented. Intrinsic factors [biofilm-associated protein, outer membrane protein A, chaperon-usher pilus, iron uptake mechanism, poly-β-(1, 6)-N-acetyl glucosamine, BfmS/BfmR two-component system, PER-1, quorum sensing] involved in biofilm production, extrinsic factors (surface property, growth temperature, growth medium) associated with the process, the impact of biofilms on high antimicrobial tolerance and regulation of the process, gene transfer within the biofilm, are elaborated. The infections associated with colonization of A. baumannii on medical devices are discussed. Each important device-related infection is dealt with and both adult and pediatric studies are separately mentioned. Furthermore, the strategies of preventing A. baumannii biofilms with antibiotic combinations, quorum sensing quenchers, natural products, efflux pump inhibitors, antimicrobial peptides, nanoparticles, and phage therapy are enumerated.

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Analysis of Antimicrobial and Antibiofilm Activity of Human Milk Lactoferrin Compared to Bovine Lactoferrin against Multidrug Resistant and Susceptible Acinetobacter baumannii Clinical Isolates

Cited by 25 publications

References 44 publications

Interaction of Acinetobacter baumannii with Human Serum Albumin: Does the Host Determine the Outcome?

Interaction of Acinetobacter baumannii with Human Serum Albumin: Does the Host Determine the Outcome?

Antibiofilm Activity of Human Milk Oligosaccharides against Multidrug Resistant and Susceptible Isolates of Acinetobacter baumannii

Convergence of Biofilm Formation and Antibiotic Resistance in Acinetobacter baumannii Infection

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