Synergetic effects of Ulva lactuca and Pterocladiella capillacea on the multidrug-resistant Klebsiella pneumoniae

Abstract

Background: The potential of marine algae as a source of antibacterial chemicals has been very promising. Numerous bioactive compounds produced by these organisms can fight off harmful microorganisms. Two marine algae (Chlorophyta: Ulva lactuca, Rhodophyta: Pterocladiella capillacea) were screened for their antibacterial activity against distinct multidrug-resistant bacteria Klebsiella pneumoniae. This efficiency is ascribed to the bioactive substances found in these algae, which have the ability to stop the growth of this harmful bacteria. Pterocladiella capillacea is a viable target for the development of novel antibacterial medications since its chemicals function by interfering with bacterial processes.

Results: A mixture of (U. lactuca + P. capillacea. + Nitrofurantoin) increased the inhibition zone on K. pneumoniae by 100%. Our docking findings demonstrated that benzo[h]quinoline, 2, 4-dimethyl-, and 4, 4'-Bis [4-methyl-2-pyrimidylsulfamido] terephthalanilide have a high affinity (-10 and - 11 respectively) to dock with the cell wall proteins of Klebsiella pneumoniae. It can cause cell lysis and death by interfering with the integrity of bacterial cell walls. Furthermore, it may disrupt DNA replication and vital bacterial enzymes. The molecule 4, 4'-Bis [4-methyl-2-pyrimidylsulfamido] terephthalanilide is a member of the sulfonamide class, which is well-known for its broad-spectrum antibacterial properties. This compound's capacity to prevent bacteria from synthesizing folic acid is the main source of its antibacterial action. Bacterial cell division and DNA synthesis depend on folic acid. The substance successfully stops bacterial growth and multiplication by blocking this pathway.

Conclusion: These two substances are interesting candidates for the development of novel antimicrobial drugs due to their efficacy against strains of bacteria that are resistant to antibiotics.

Keywords: Klebsiella pneumoniae; Pterocladiella capillacea; Ulva lactuca; Drug resistant; Synergetic effects.

Fig. 1

Phylogenetic tree of partial 16s rRNA showing the phylogenetic position of against K. pneumoniae (GRA1) (written in brown) compared with other related K. pneumoniae from the Gene Bank, including the most common reference strain ATCC 13,883(witten in blue). Bootstrap values for nodes are shown in the tree

Fig. 2

Isolated marine algal strains (A) Ulva Lactuca, B Pterocladiella capillacea

Fig. 3

MIC value of U. lactuca A Box plot for the ethanolic and methanolic extract, panel B is the corresponding plate for ethanolic extracts and panel C is the corresponding plate for methanolic extract against Klebsiella pneumoniae; symbols on plates is for the used concentration 1: 500 mg/ml, 2: 250 mg/ml, 3: 125 mg/ml, 4: 62.5 mg/ml, 5: 31.25 mg/ml, 6: Negative control (5% DEMSO)

Fig. 4

MIC value of P. capillacea, A Box plot for the ethanolic and methanolic extract, panel B is the corresponding plate for ethanolic extracts and panel C is the corresponding plate for methanolic extract against K. pneumoniae; symbols on plates is for the used concentration 1: 500 mg/ml, 2: 250 mg/ml, 3: 125 mg/ml, 4: 62.5 mg/ml, 5: 31.25 mg/ml, 6: Negative control (5% DEMSO)

Fig. 5

Synergetic inhibition effect of Ulva lactuca and Pterocladiella capillacea ethanolic extracts single or in combination with antibiotic (Nitrofurantion 300 μg) against K. pneumoniae strain GRA1; panel A is the box plot of the adjusted p value calculated. panel B is the corresponding plate for the synergesic effect; symbols on the agar plate indicate the used extract and/or antibiotics 1: U. lactuca ethanolic extract, 2: Pterocladiella capillacea ethanolic extract, 3: U. lactuca + Pterocladiella capillacea, 4: U. lactuca + Nitrofurantion, 5: Pterocladiella capillacea. + Nitrofurantion, 6: U. lactuca + Pterocladiella capillacea. + Nitrofurantion, 7: Negative control (5% DEMSO), 8: Positive control Nitrofurantion 300 μg

Fig. 6

GC-Mas representation of bioactive compounds extracted from: A U. lactuca, B P. capillacea

Fig. 7

3D and 2D interactions for Benzo[h]quinoline_2_4_dimethyl_ (left panel) and 4,4'-Bis[4-methyl-2-pyrimidylsulfamido]terephthalanilide (right panel) with each protein

Fig. 8

In silico toxicity of Benzo[h]quinoline_2_4_dimethyl_ using https://tox.charite.de/protox3/index.php?site=home

Fig. 9

In silico toxicity of 4,4’-Bis[4-methyl-2-pyrimidylsulfamido]terephthalanilide using https://tox.charite.de/protox3/index.php?site=home