Investigation of antibacterial mode of action for traditional and amphiphilic aminoglycosides

Udumula, Venkatareddy; Ham, Young Wan; Fosso, Marina Y.; Chan, Ka Yee; Rai, Ravi; Zhang, Jianjun; Li, Jie; Chang, Cheng‐Wei Tom

doi:10.1016/j.bmcl.2013.01.073

Cited by 22 publications

(20 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…115 With the aim of investigating the mode of action of antibacterial amphiphilic AGs, the Garneau-Tsodikova and Fridman groups showed that amphiphilic AGs in the form of 6"-thioether TOB analogues target the bacterial membrane rather than the traditional bacterial ribosome. 105 Similar results were also observed by the Chang 116 and the Mingeot-Leclercq 117 groups, who synthesized 5"-derivatized NEO as well as 3’- and 6-modified NEA, respectively.…”

Section: Aminoglycosides As Antifungal Agentssupporting

confidence: 78%

New trends in the use of aminoglycosides

Fosso

2014

Med. Chem. Commun.

Self Cite

100

View full text Add to dashboard Cite

Despite their inherent toxicity and the acquired bacterial resistance that continuously threaten their long-term clinical use, aminoglycosides (AGs) still remain valuable components of the antibiotic armamentarium. Recent literature shows that the AGs’ role has been further expanded as multi-tasking players in different areas of study. This review aims at presenting some of the new trends observed in the use of AGs in the past decade, along with the current understanding of their mechanisms of action in various bacterial and eukaryotic cellular processes.

show abstract

Section: Aminoglycosides As Antifungal Agentssupporting

confidence: 78%

New trends in the use of aminoglycosides

Fosso

2014

Med. Chem. Commun.

Self Cite

100

View full text Add to dashboard Cite

show abstract

“…Several observations indicate membrane perturbation as the primary antibacterial action of these compounds and not ribosome interaction to cause protein translation misreading. 4,10,11,23,28 …”

Section: Amphiphilic Aminoglycosidesmentioning

confidence: 99%

Antifungal amphiphilic aminoglycosides

Chang

Takemoto

2014

Med. Chem. Commun.

View full text Add to dashboard Cite

The attachment of alkyl and other hydrophobic groups to traditional antibacterial kanamycins and neomycins creates amphiphilic aminoglycosides with altered antimicrobial properties. In this review, we summarize the discovery of amphiphilic kanamycins that are antifungal, but not antibacterial, and that inhibit the growth of fungi by perturbation of plasma membrane functions. With low toxicities against plant and mammalian cells, they appear to specifically target the fungal plasma membrane. These new antifungal agents offer new options for fighting fungal pathogens and are examples of reviving old drugs to confront new therapeutic challenges.

show abstract

“…Recently,a mphiphilic aminoglycosides (AAGs) have emerged as as ource of antibacterial agents to combat bacterial resistance. [5][6][7][8][9][10][11][12][13][14] Modeof-action studies have shown that AAGs can show different modes of action [9,[11][12][13] to AGs, which bind to the 30S ribosomal subunit, thereby leading to the disruption of protein synthesis. [15] Fori nstance,i tw as shown that the antibacterial effect of an eamine-based AAGa gainst P. aeruginosa was caused by changes in membrane depolarization and permeability and not by inhibition of protein synthesis.…”

mentioning

confidence: 99%

Amphiphilic Tobramycins with Immunomodulatory Properties

et al. 2015

View full text Add to dashboard Cite

Amphiphilic aminoglycosides (AAGs) are an emerging source of antibacterials to combat infections caused by antibiotic-resistant bacteria. Mode-of-action studies indicate that AAGs predominately target bacterial membranes, thereby leading to depolarization and increased permeability. To assess whether AAGs also induce host-directed immunomodulatory responses, we determined the AAG-dependent induction of cytokines in macrophages in the absence or presence of lipopolysaccharide (LPS). Our results show for the first time that AAGs can boost the innate immune response, specifically the recruitment of immune cells such as neutrophils required for the resolution of infections. Moreover, AAGs can selectively control inflammatory responses induced in the presence of endotoxins to prevent septic shock. In conclusion, our study demonstrates that AAGs possess multifunctional properties that combine direct antibacterial activity with host-directed clearance effects reminiscent of those of host-defense peptides.

show abstract

Investigation of antibacterial mode of action for traditional and amphiphilic aminoglycosides

Cited by 22 publications

References 19 publications

New trends in the use of aminoglycosides

New trends in the use of aminoglycosides

Antifungal amphiphilic aminoglycosides

Amphiphilic Tobramycins with Immunomodulatory Properties

Contact Info

Product

Resources

About