Bioguided Isolation of Antibiofilm and Antibacterial Pregnane Glycosides from Caralluma quadrangula: Disarming Multidrug-Resistant Pathogens

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Acinetobacter baumannii (MDRAB) present a serious challenge because of their capability to cause biofilm resistance to commonly used antibiotics producing chronic infections and hindering the process of wound healing. In the current study, we investigated the antibacterial activity of Caralluma quadrangula extracts (MeOH, and its fractions CH2Cl2 and n-butanol) against multidrug-resistant MRSA USA300 and A. baumannii AB5057. In vitro, the MeOH extract and both fractions of C. quadrangula significantly inhibited biofilm formation and disrupted previously established biofilm by MRSA and MDRAB at all the tested concentrations (0.625, 0.313, and 0.156 mg/mL). In vivo, C. quadrangula extracts successfully decreased bacterial loads in MRSA-infected skin lesions in mice. Four pregnane glycosides and one flavone glycoside were isolated from the bioactive n-butanol fraction. The isolated compounds (Rus A–E) were tested for their biofilm inhibition and biofilm detachment activities. The results revealed that Rus C was the most active compound (IC50 = 0.139 mmole), while Rus E was the least active (IC50 = 0.818 mmole). These results support the potential use of C. quadrangula extracts or their isolated compounds for hindering the biofilm attachment and the virulence of MRSA and MDRAB and their application as a topical antimicrobial preparation for MRSA skin infections.

Out of control: The need for standardised solvent approaches and data reporting in antibiofilm assays incorporating dimethyl-sulfoxide (DMSO)

“…However, when the concentration of DMSO used to solubilise treatments was provided, it can be reasonably assumed that the same DMSO concentration was used for the control [ [84] , [85] , [86] ] and vice versa [ 82 , 87 ]. More problematic were studies wherein both solvent (test solution) and control DMSO concentrations were not clearly specified [ 45 , 73 , 81 , 88 ]. While statements were occasionally included to imply that the experiments were controlled to a degree, greater transparency regarding the control conditions and any findings relative to the treatments would be best.…”

Exploring the Antivirulence Activity of Pulverulentone A, a Phloroglucinol-Derivative from Callistemon citrinus Leaf Extract, against Multi-Drug Resistant Pseudomonas aeruginosa

“…The global spread of microbial resistance makes it urgent to find an alternative way to control infections [ 25 ]. Antivirulence therapy involves the attenuation of microbial virulence factors and hence microbial pathogenicity, enhancing the clearance of the infection by the immune system [ 26 ].…”

“…Initially, all P. aeruginosa isolates were screened for their ability to form biofilm. Each isolate was allowed to form biofilm according to the method described by [ 25 , 44 ] with slight modifications. Briefly, overnight culture of each test isolate was prepared in TSB according to the above mentioned growth conditions: the turbidity of each culture was adjusted to OD 600 of 0.1–0.125, then diluted 1:100 in fresh TSB.…”

Luteolin 4′-Neohesperidoside Inhibits Clinically Isolated Resistant Bacteria In Vitro and In Vivo

“…Luteolin-4′- O -neohesperidoside (L4N), i.e., luteolin-4′- O -[α-(L-rhamnopyranosyl-(1→2)- β -D-glucopyranoside)], was previously isolated from the genus Caralluma , showing significant anti-inflammatory and antinociceptive actions [ 9 ], and it also showed antibiofilm activity against an MRSA skin infection model [ 10 ]. Luteolin showed potent antimicrobial activity against E. coli , K. pneumoniae , MRSA, Trueperella pyogenes , and Mycobacterium tuberculosis .…”

“…Methicillin-resistant Staphylococcus aureus (MRSA) is a prominent agent of community- and health-care-associated infections (CAIs and HAIs) [ 9 ], ranging from superficial soft tissue infections (SSTI) to toxic shock syndrome (TSS), sepsis, and death [ 10 ].…”