Amide side chain amphiphilic polymers disrupt surface established bacterial bio-films and protect mice from chronic Acinetobacter baumannii infection

Uppu, Divakara S. S. M.; Samaddar, Sandip; Ghosh, Chandradhish; Krishnamoorthy, P.; Shome, Bibek Ranjan; Haldar, Jayanta

doi:10.1016/j.biomaterials.2015.09.042

Cited by 79 publications

(91 citation statements)

References 62 publications

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“…We have reported the synthesis and characterization of cationic-amphiphilic macromolecules based on poly(isobutylene- alt - N -alkyl maleimide) backbone previously [ 30 – 32 ]. The detailed synthetic protocols and complete characterization have been reported previously [ 30 – 32 ].…”

Section: Resultsmentioning

confidence: 99%

Membrane-active macromolecules kill antibiotic-tolerant bacteria and potentiate antibiotics towards Gram-negative bacteria

et al. 2017

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Chronic bacterial biofilms place a massive burden on healthcare due to the presence of antibiotic-tolerant dormant bacteria. Some of the conventional antibiotics such as erythromycin, vancomycin, linezolid, rifampicin etc. are inherently ineffective against Gram-negative bacteria, particularly in their biofilms. Here, we report membrane-active macromolecules that kill slow dividing stationary-phase and antibiotic tolerant cells of Gram-negative bacteria. More importantly, these molecules potentiate antibiotics (erythromycin and rifampicin) to biofilms of Gram-negative bacteria. These molecules eliminate planktonic bacteria that are liberated after dispersion of biofilms (dispersed cells). The membrane-active mechanism of these molecules forms the key for potentiating the established antibiotics. Further, we demonstrate that the combination of macromolecules and antibiotics significantly reduces bacterial burden in mouse burn and surgical wound infection models caused by Acinetobacter baumannii and Carbapenemase producing Klebsiella pneumoniae (KPC) clinical isolate respectively. Colistin, a well-known antibiotic targeting the lipopolysaccharide (LPS) of Gram-negative bacteria fails to kill antibiotic tolerant cells and dispersed cells (from biofilms) and bacteria develop resistance to it. On the contrary, these macromolecules prevent or delay the development of bacterial resistance to known antibiotics. Our findings emphasize the potential of targeting the bacterial membrane in antibiotic potentiation for disruption of biofilms and suggest a promising strategy towards developing therapies for topical treatment of Gram-negative infections.

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Section: Resultsmentioning

confidence: 99%

Membrane-active macromolecules kill antibiotic-tolerant bacteria and potentiate antibiotics towards Gram-negative bacteria

et al. 2017

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“…One important MDR Gram-negative bacteria is Acinetobacter baumannii , which is known to be associated with recent battle wounds and is resistant to almost all available antibiotics 3 . The presence of biofilms at the injured foci has been reported 4,5 and is believed to exacerbate the tolerance to antibiotics and host defense 6,7 , causing persistent infections 8,9 . Therefore, there is a pressing need for the development of alternative treatments.…”

Section: Introductionmentioning

confidence: 99%

<em>In Vivo</em> Investigation of Antimicrobial Blue Light Therapy for Multidrug-resistant <em>Acinetobacter baumannii</em> Burn Infections Using Bioluminescence Imaging

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et al. 2017

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Burn infections continue to be an important cause of morbidity and mortality. The increasing emergence of multidrug-resistant (MDR) bacteria has led to the frequent failure of traditional antibiotic treatments. Alternative therapeutics are urgently needed to tackle MDR bacteria. An innovative non-antibiotic approach, antimicrobial blue light (aBL), has shown promising effectiveness against MDR infections. The mechanism of action of aBL is not yet well understood. It is commonly hypothesized that naturally occurring endogenous photosensitizing chromophores in bacteria (e.g., iron-free porphyrins, flavins, etc.) are excited by aBL, which in turn produces cytotoxic reactive oxygen species (ROS) through a photochemical process. Unlike another light-based antimicrobial approach, antimicrobial photodynamic therapy (aPDT), aBL therapy does not require the involvement of an exogenous photosensitizer. All it needs to take effect is the irradiation of blue light; therefore, it is simple and inexpensive. The aBL receptors are the endogenous cellular photosensitizers in bacteria, rather than the DNA. Thus, aBL is believed to be much less genotoxic to host cells than ultraviolet-C (UVC) irradiation, which directly causes DNA damage in host cells. In this paper, we present a protocol to assess the effectiveness of aBL therapy for MDR Acinetobacter baumannii infections in a mouse model of burn injury. By using an engineered bioluminescent strain, we were able to noninvasively monitor the extent of infection in real time in living animals. This technique is also an effective tool for monitoring the spatial distribution of infections in animals.

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“…Maleic anhydride-based amphiphillic polymers, containing amide side chains, disrupt surface established A. baumannii biofilms. These polymers also reduce the bacterial count in mice with chronic burn-wound infection [88]. Similar observation was seen with methacrylate polymers containing a 2-aminoimidazole subunit [112].…”

Section: Acinetobacter Biofilm Control Through Nanomaterialsmentioning

confidence: 67%

“…Both organic and inorganic nanoparticles are reported to have antibacterial and anti-biofilm potencies [14,85,86,87,88,89]. These are also used as surface-coating and drug-delivery agents [90,91] and thus offer a very promising alternative to conventional methods of biofilm control.…”

Section: Acinetobacter Biofilm Control Through Nanomaterialsmentioning

confidence: 99%

Nanoparticles for Control of Biofilms of Acinetobacter Species

et al. 2016

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Biofilms are the cause of 80% of microbial infections. Acinetobacter species have emerged as multi- and pan-drug-resistant bacteria and pose a great threat to human health. These act as nosocomial pathogens and form excellent biofilms, both on biotic and abiotic surfaces, leading to severe infections and diseases. Various methods have been developed for treatment and control of Acinetobacter biofilm including photodynamic therapy, radioimmunotherapy, prophylactic vaccines and antimicrobial peptides. Nanotechnology, in the present scenario, offers a promising alternative. Nanomaterials possess unique properties, and multiple bactericidal mechanisms render them more effective than conventional drugs. This review intends to provide an overview of Acinetobacter biofilm and the significant role of various nanoparticles as anti-biofouling agents, surface-coating materials and drug-delivery vehicles for biofilm control and treatment of Acinetobacter infections.

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Amide side chain amphiphilic polymers disrupt surface established bacterial bio-films and protect mice from chronic Acinetobacter baumannii infection

Cited by 79 publications

References 62 publications

Membrane-active macromolecules kill antibiotic-tolerant bacteria and potentiate antibiotics towards Gram-negative bacteria

Membrane-active macromolecules kill antibiotic-tolerant bacteria and potentiate antibiotics towards Gram-negative bacteria

<em>In Vivo</em> Investigation of Antimicrobial Blue Light Therapy for Multidrug-resistant <em>Acinetobacter baumannii</em> Burn Infections Using Bioluminescence Imaging

Nanoparticles for Control of Biofilms of Acinetobacter Species

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